Safety and Feasibility of Adipose Derived Regenerative Cells (ADRCs) in the Treatment of Deep Partial Thickness and Full Thickness Thermal Wounds (RELIEF)
Phase: NA
Conditions: Thermal Burn
Sponsor: Cytori Therapeutics

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 1 of 48 
Date: 
May 14, 2018 
 
 
 
Safety and Feasibility of Adipose Derived Regenerative Cells (ADRCs) in the 
Treatment of Deep Partial Thickness and Full Thickness Thermal Wounds 
(RELIEF) 
 
 
RELIEF Trial 
Version 04 
14 May 2018 
 
Cytori Therapeutics, Inc.  
3020 Callan Road 
San Diego, CA  92121  
USA 
Phone: +1-858-458-0900 
www.cytori.com 
 
 
 
CONFIDENTIAL 
The information contained herein is confidential and proprietary information of Cytori Therapeutics, Inc. It is intended solely for the use of 
Cytori Therapeutics, Inc. and its designated clinical Investigators or Institutional Review Committees, and others directly involved in this 
clinical investigation who are bound to the confidentiality obligations of a Confidentiality Agreement between Cytori Therapeutics and the 
Investigators participating in this study. If you are not the designated recipient, please call us (collect) immediately at (858) 458-0900 to 
arrange for the return of this information. Any review, dissemination, distribution, copying, or use of this information by anyone other than 
the designated recipient(s) is strictly prohibited. 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 2 of 48 
Date: 
May 14, 2018 
 
 
Contents 
PROTOCOL APPROVAL FORM 
5 
INVESTIGATOR STATEMENT PAGE 
6 
RELIEF TRIAL PROTOCOL SUMMARY 
8 
ABBREVIATIONS 
11 
1 OBJECTIVE 
12 
2 BACKGROUND 
12 
2.1 
Wounds 
12 
2.2 
Pre-Clinical Data 
12 
2.3 
Clinical Data 
13 
3 RATIONALE 
14 
4 STUDY DESIGN 
14 
4.1 
Study Overview 
14 
4.2 
Study Population 
15 
4.3 
Sample Size 
15 
4.4 
Clinical Sites 
16 
4.5 
Study Duration 
16 
4.6 
Study Endpoints 
16 
4.6.1 
Primary Endpoints 
16 
4.6.2 
Key Secondary Endpoints 
16 
4.6.3 
Exploratory Endpoints 
17 
4.7 
Inclusion and Exclusion Criteria 
17 
4.7.1 
Inclusion Criteria 
17 
4.7.2 
Exclusion Criteria 
18 
5 ENROLLMENT 
18 
5.1 
Subject Enrollment 
18 
5.2 
Randomization and Subject Identification 
19 
5.3 
Stopping Rules 
19 
5.4 
Blinding Procedures and Safeguards 
19 
5.5 
Subject Withdrawal and Replacement 
19 
6 CELUTION® SYSTEM 
20 
6.1 
Celution® System Description 
20 
6.2 
Device Characterization and Intended Use 
20 
6.3 
Contraindications 
20 
6.4 
Intended Clinical Performance 
20 
6.5 
Celution® System Output: Physical, Chemical, and Mechanism of Action 
20 
6.6 
Proposed Mechanism of Action of ADRCs 
21 
7 STUDY TREATMENTS 
21 
7.1 
Product Description - ADRCs 
21 
7.1.1 
Treatment Dose Control 
22 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 3 of 48 
Date: 
May 14, 2018 
7.2 
Study Treatment Sterility Testing 
22 
7.3 
ADRC Characterization 
23 
8 STUDY ASSESSMENTS 
24 
8.1 
Medical History, Physical Examination & Vital Signs 
24 
8.2 
Adverse Events 
24 
8.3 
Burn Evaluations 
24 
8.4 
Prior and Concomitant Medications 
25 
8.4.1 
Prohibited Medications 
25 
8.5 
Laboratory Procedures 
25 
8.6 
STUDY VISIT REQUIREMENTS 
25 
8.6.1 
Day -2 to Day -1: Screening 
25 
8.7 
Procedure Day (Day 1) 
26 
8.7.1 
Fat Harvest 
26 
8.7.2 
Digital Photography 
28 
8.7.3 
ADRCs Delivery 
28 
8.8 
Post-ADRC Administration time of first dressing change and Day 10 (±2 days)* 
29 
8.9 
Post-ADRC Administration Follow-up visits:  Weeks 2 (±3 days), 3 (±3 days) and 4 (±3 days) 
29 
8.10 
Post-ADRC Administration Follow-up visits: Weeks 8 (±7 days), 12 (±7 days), 26 (±14 days), and 52 
(±21 days) 
30 
8.11 
Early Termination Evaluation 
30 
9 RISK/BENEFIT ANALYSIS 
31 
9.1 
Context of the proposed investigation: 
31 
9.2 
Assessment of risks of the proposed Investigation 
32 
9.3 
Risks 
32 
9.4 
Intravenous Delivery Risk Analysis and Management 
32 
9.5 
Celution® System and Delivery Device Risk Analysis and Management 
32 
9.6 
Fat Harvest Risk Analysis 
33 
9.6.1 
Fat Harvest Risk Management 
33 
9.7 
Overall Study Risk Management 
34 
9.8 
Assessment of the Benefits of the Proposed Investigation 
35 
9.9 
Consideration of Patient Preference information 
35 
9.10 
Assessment of Uncertainty 
35 
9.11 
Conclusions 
35 
10 STATISTICAL METHODS AND DATA ANALYSIS 
36 
10.1 
General Considerations 
36 
10.2 
Determination of Sample Size 
36 
10.3 
Data Analyses 
36 
10.3.1 
Primary Endpoint Analysis 
36 
10.3.2 
Key Secondary and Exploratory Endpoint Analysis 
37 
10.4 
Background, Demographic and Concomitant Medication Analyses 
37 
10.5 
Withdrawal, ITT, PTE 
37 
10.6 
Handling of Missing Data 
37 
10.7 
Protocol Deviations 
38 
10.8 
Data Monitoring Committee 
38 
11 ADVERSE EVENTS / SERIOUS ADVERSE EVENTS 
38 
11.1 
Definitions 
38 
11.2 
Procedures for AE Reporting 
39 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 4 of 48 
Date: 
May 14, 2018 
12 EMERGENCY DEVIATION FROM THE PROTOCOL 
39 
13 REGULATORY OBLIGATIONS AND STUDY REQUIREMENTS 
39 
13.1 
FDA and Institutional Review Board Approval 
39 
13.2 
Informed Consent 
40 
13.3 
Monitoring Procedures and Data Management 
40 
13.3.1 
Site Qualification 
40 
13.3.2 
Site Training 
40 
13.3.3 
Monitoring 
40 
13.3.4 
Reporting Requirements 
40 
13.3.5 
Data Management 
40 
13.4 
Study Center and Investigator Requirements 
41 
13.4.1 
Study Center Requirements 
41 
14 PUBLICATIONS 
42 
15 APPENDIX A:  SCHEDULE OF PROCEDURES 
43 
16 REFERENCES 
46 
 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 5 of 48 
Date: 
May 14, 2018 
PROTOCOL APPROVAL FORM 
 
Study Title: 
Safety and Feasibility of Adipose Derived Regenerative Cells (ADRCs) in the 
Treatment of Deep Partial Thickness and Full Thickness Thermal Wounds (RELIEF) 
Short Title: 
RELIEF Trial 
 
Protocol Date: 
24 April, 2018 
 
 
This study protocol was subjected to critical review. The information it contains is consistent with the 
sponsor’s current knowledge of the risks and benefits of the investigational product, as well as with the 
moral, ethical and scientific principles governing clinical research as set out in the Declaration of 
Helsinki, as amended in 2008, and the Good Clinical Practice (GCP) Consolidated Guidance in guidelines 
of the International Conference on Harmonization (ICH) E2 & E6, and 21CFR 11, 50, 56, 812, 814 and 
820. The study will also be carried out in keeping with all applicable laws, rules, and regulations. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Terrie Heidemann 
 
 
 
 
Date (dd/mmm/yyyy) 
Senior Manager, Regulatory & Quality Assurance 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Marc H. Hedrick, MD 
 
 
 
Date (dd/mmm/yyyy) 
Chief Executive Officer and  
Chief Medical Officer 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 6 of 48 
Date: 
May 14, 2018 
INVESTIGATOR STATEMENT PAGE 
 
Study Sponsor: 
Cytori Therapeutics, Inc.  
Clinical Trial: 
RELIEF Trial 
Date of Protocol: 
24 April, 2018 
 
Study Title: Safety and Feasibility of Adipose Derived Regenerative Cells (ADRCs) in the Treatment 
of Deep Partial Thickness and Full Thickness Thermal Wounds (RELIEF) 
 
The information contained in this document and all information provided to you related to this protocol 
are the confidential and proprietary information of Cytori Therapeutics, Inc. (Sponsor) and except as may 
be required by federal, state or local laws or regulations, may not be disclosed to others without prior 
written permission of Sponsor. The Principal Investigator at each site may, however, disclose such 
information to supervised individuals working on the protocol, provided such individuals agree to be 
bound to maintain the confidentiality of such protocol information. 
I agree to abide by the statement of confidentiality. 
I agree to conduct the study according to this protocol. Any changes in procedure will only be made if 
necessary to protect the safety, rights, or welfare of subjects. 
I agree to comply with the current ICH, GCP and CFR Guidelines.  
I agree to conduct the study in person or to supervise the study. 
I agree to ensure that all who assist me in the conduct of the study have access to the study protocol and 
any amendments and are aware of their obligations. 
I agree to conduct the investigation in accordance with the agreement, the investigational plan, Part 812 
and other applicable FDA regulations, and conditions of approval imposed by the reviewing IRB and 
FDA. 
I agree to supervise all testing of the device involving human subjects. 
I agree to ensure that the requirements for obtaining informed consent are met. 
I agree to provide sufficient and accurate financial disclosure information and update information if any 
relevant changes occur during the investigation and for one year following the completion of the study. 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator (Print Name and Title) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator (Signature) 
 
 
 
Date 
(dd/mmm/yyyy) 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 7 of 48 
Date: 
May 14, 2018 
STUDY CONTACTS 
 
 
RELIEF Trial Sponsor 
 
Cytori Therapeutics, Inc. 
3020 Callan Road 
San Diego, CA  92121, USA 
Toll Free (US): (877) 470-8000 
Fax: (858) 875-5065 
 
 
Medical Monitor 
 
Marc H. Hedrick MD 
Chief Executive and Chief Medical Officer 
Cytori Therapeutics, Inc. 
3020 Callan Road 
San Diego, CA 92121, USA 
Phone: (858) 458-0900 
 
   
Safety (SAE) Notifications: 
24 Hour Study Contacts: 
Telephone:  (858) 205-5824 
Cell: 914-513-6459 
FAX: 858-875-5204 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 8 of 48 
Date: 
May 14, 2018 
RELIEF TRIAL PROTOCOL SUMMARY 
Title 
Safety and Feasibility of Adipose Derived Regenerative Cells (ADRCs) in the 
Treatment of Deep Partial Thickness and Full Thickness Thermal Wounds 
(RELIEF) 
Test Product 
Celution® System used for processing of Autologous Adipose-Derived Regenerative 
Cells (ADRCs) 
Objective 
The primary objective of the protocol is to evaluate preliminary safety and feasibility 
of ADRCs via intravenous delivery in the treatment of deep partial and full thickness 
thermal wounds.  
Design 
A prospective, open-label, parallel group, usual care controlled, multi-center 
randomized (2:1, active: usual care alone) safety and feasibility study targeting 
thermal burns. Subjects will have at least one deep partial or full thickness burn 
wound of ≥ 250 cm2 that is to be autografted with a meshed split thickness skin graft 
(STSG) Subjects randomized to ADRCs will undergo small volume fat harvest (100 
to 150 mL) performed under general anesthesia during scheduled burn surgery 
followed by peripheral intravenous delivery of ADRCs within 4 hours of completion 
of Celution® processing. Harvested tissue will be processed in the Celution® System 
to isolate and concentrate ADRCs. Subjects randomized to usual care will not 
undergo a fat harvesting procedure.  
Sample Size 
Up to 15 subjects will be enrolled. Each subject will contribute up to three qualified 
wound areas for the analysis.  
Enrollment 
The 1st 5 subjects enrolled in active treatment will be observed for adverse events 
over a 7 day period. If no SAEs occur during that period, for that individual subject, 
the next subject enrolled in active treatment may be entered with the same 7 day 
observation period. The safety results of the first 5 subjects will be reviewed by the 
DMC and their evaluation will be used in conjunction with the clinical data collected 
to date, and if appropriate, to potentially remove the staggering approach to the 
study. Enrollment after the first 5 subjects enrolled in active treatment may continue 
only after the DMC has completed its safety review and recommends continuation.  
Study 
Location 
Up to 10 regional burn centers in the US 
Indication 
Celution® System is intended for the preparation of autologous adipose-derived 
regenerative cells (ADRCs) for intravenous use as an adjunct to autologous split 
thickness skin grafts used in the current standard treatment of full thickness and deep 
partial thickness thermal burn injuries 
Post 
Procedure 
Evaluations 
Evaluations at early dressing changes (time of first dressing change, day 10 (±2) days 
and weeks 2 (±3 days), 3 (±3 days), 4 (±3 days), 8 (±7 days), 12 (±14 days), 26 (±14 
days) and 52 (±21 days) post-grafting 
Treatment 
Arm 
Adjunct to thermal burn skin wound coverage with autologous meshed split 
thickness skin graft (STSG) delivered intravenously on the same day as STSG.  
Dose: 20 x 106 ADRCs 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 9 of 48 
Date: 
May 14, 2018 
Primary 
Endpoint 
Safety and Feasibility 
 
Safety will be evaluated based on the incidence, type and seriousness of adverse 
events related to the IV administration of test substance as well as the low 
volume lipoharvest procedure. 
 
Feasibility will be determined as the ability to obtain > 100 mL adipose tissue, 
obtain ≥ 20 x 106 ADRCs, and deliver the prepared cell dose. 
 
Key 
Secondary 
Endpoints 
 Percent epithelialization of the graft at time of first dressing change, day 10 and 
weeks 2, 3 and 4 post grafting (assessed by surgeon visual evaluation and blinded 
independent review of standardized photographs) 
 Percent take of the graft at time of first dressing change and day 10 and weeks 2, 
3 and 4  
 Percent of group with complete wound healing at weeks 2, 3, 4, 8 and 12 
Exploratory 
Endpoints 
 Transepithelial water loss at weeks 2, 3 and 4 to be performed at 2 different sites 
within the wound (central and peripheral) 
 Wound pain VAS (visual analogue scale) at time of first dressing change and day 
10 and weeks 2, 3 and 4 
 Pruritis VAS at weeks 3, 4, 8, 12, 26 and 52  
 Patient and Observer Scar Assessment Scale (v2.0) at weeks 3, 4, 8, 12, 26 and 52 
 Skin elasticity measurement at weeks 12, 26 and 52 
 Vancouver Scar Scale at weeks 12, 26 and 52  
 Skin pigmentation and hardness at weeks 12, 26 and 52 
 ADRC cell population subtypes (FACS) 
 Biomarkers related to burn injury (such as C-reactive protein (CRP), IL-6, IL8, 
IL1β, interleukin-1 receptor antagonist (IL-1ra); neutrophil gelatinase-associated 
lipocalin (NGAL); Tumor Necrosis Factor-α (TNFα),  and tumor necrosis factor 
receptor 1a (TNFR-1a)) and related to scarring (such as  amino-terminal 
propeptide of type III procollagen, (PIIINP), TIMP1, MMP2, MMP9 and VEGF-
A) will be collected at baseline (prior to treatment), days 6, and 10 and weeks 2, 
3, 4, 8, and 12 post ADRC administration. Serum sample will be collected from 4 
to 5 ml of whole blood that is centrifuged, separated into 500-µL aliquots, and 
stored at  -80°C at the clinical site serum bank or central lab until use.  
 Serum biomarkers will be measured using commercial Enzyme-Linked 
ImmunoSorbent Assay (ELISA).  
Statistics 
The intent-to-treat (ITT) population will include all randomized subjects. 
Randomization will occur on the STSG procedure day prior to liposuction.  
The per-treatment-evaluable (PTE) population will include all enrolled subjects who 
have day 6 follow-up information available. 
The groups compared will be the subjects receiving ADRCs and STSG and the usual 
care controlled subjects (both grouped and stratified by mesh size). Analysis will be 
performed by a one way ANOVA. 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 10 of 48 
Date: 
May 14, 2018 
Inclusion  & 
Exclusion 
Criteria 
 
 
Inclusion Criteria 
1. Males or females age ≥ 18 to ≤ 65  
2. BMI > 20 kg/m2 
3. Burn TBSA 20% - 50% 
4. At least one deep partial thickness and/or full thickness thermal burn ≥ 250 
cm2 on the arms, legs, back, abdomen or chest that is anticipated to be 
covered with a meshed autologous STSG and that has not been treated 
previously with a biologic dressing such as Alloderm® or Integra® 
5. Ability to safely undergo tissue harvest that is anticipated to yield >150 mL 
of adipose tissue at a site that is free from infection 
6. Donor site availability for skin graft harvest 
7. Able to provide written informed consent signed by either the patient or their 
legally authorized representative 
8. Women and men of child-bearing potential agreeing to use contraception 
during the study. Acceptable methods include surgical sterility, IUDs, 
hormonal contraception or double barrier methods. 
 
Exclusion Criteria 
 
1. Subjects with burns > 3rd degree (i.e. involvement of deeper tissues, such as 
muscle, tendons, or bone) 
2. Subjects with electrical or chemical burns 
3. Subjects with significant inhalation injuries necessitating intubation and 
mechanical ventilation or requiring > 50% FI02 on a continuous basis to 
maintain oxygenation (02 sat > 90%) 
4. In the opinion of treating physician, patient not expected to survive beyond 
30 days 
5. Pre-existing condition requiring current use of immunosuppressive 
medication or systemic steroids 
6. Pregnant or lactating status. Pregnancy as determined by a positive 
pregnancy test at screening or baseline 
7. Known history of HIV infection, or active Hepatitis B or active Hepatitis C 
infection 
8. Cancer requiring chemotherapy or radiation within previous 6 months or 
resection within the last 5 years (other than basal cell carcinoma) 
9. Known chronic renal failure (serum creatinine > 2 mg/dL) or chronic liver 
disease 
10. Pre-existing medical conditions that would interfere with wound healing 
(i.e.,  diabetic patients with Hemoglobin A1c ≥8.0%, malignancy, 
autoimmune disease) 
11. Subjects with psychiatric conditions that are anticipated to result in protocol 
noncompliance 
12. Chronic illicit drug or alcohol abuse that is anticipated to interfere with 
patient compliance with the protocol 
13. Participation in another clinical trial within 60 days of the screening visit 
14. Any concurrent disease or condition that, in the opinion of the investigator, 
would make the patient unsuitable for participation in the study 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 11 of 48 
Date: 
May 14, 2018 
ABBREVIATIONS 
ADRC  
Adipose-Derived Regenerative Cells 
ADSC  
Adipose-Derived Stem Cells 
AE 
 
Adverse Event 
BARDA 
Biomedical Advanced Research and Development Authority  
CFU-F  
Colony Forming Units Fibroblast 
CRF 
 
Case Report Form 
DMC             Data Monitoring Committee 
DNase  
Deoxyribonuclease 
ET 
 
Early Termination 
FDA  
Food and Drug Administration 
GCP  
Good Clinical Practice 
HIV 
 
Human Immunodeficiency Virus 
ICH 
 
International Conference on Harmonization 
ID 
 
Identification 
IRB/EC 
Institutional Review Board/Ethic Committee 
ITT 
 
Intent-to-Treat 
LVL 
 
Low Volume Lipoharvest 
PBS 
 
Phosphate Buffered Saline 
PI 
 
Principal Investigator 
POSAS 
Patient and Observer Scar Assessment Scale 
PTE 
 
Per-Treatment-Evaluable 
SAE   
Serious Adverse Event  
STSG  
Split Thickness Skin Graft 
SAP 
 
Statistical Analysis Plan 
SD 
 
Standard Deviation 
SOC  
Standard of Care 
SVF 
 
Stromal Vascular Fraction 
TBSA  
Total Body Surface Area 
TF 
 
Tumescent Fluid 
UADE  
Unanticipated Adverse Device Effects 
VAS  
Visual Analog Scale 
VSS 
 
Vancouver Scar Scale 
WHO  
World Health Organization 
 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 12 of 48 
Date: 
May 14, 2018 
1 
OBJECTIVE 
The objective of the protocol is to evaluate preliminary safety and feasibility of adipose-derived 
regenerative cells (ADRCs) delivered intravenously for the treatment of full thickness and deep partial 
thickness thermal wounds in addition to standard of care. 
2 
BACKGROUND 
2.1 
Wounds 
Wound healing is a complex multifactorial process involving the interaction of inflammation, granulation 
tissue formation, re-epithelialization, and angiogenesis. For deep partial thickness and full thickness 
burns, acute burn management involves multiple activities including protecting the wound from further 
injury, initial cleansing and debridement, and determination of dressings with or without a topical 
antimicrobial agent. Fluid resuscitation, prevention of hypothermia and pain management are also critical 
aspects of management. Surgical procedures involve escharectomy with further debridement and 
determination of skin grafting (often autologous split thickness skin graft (STSG) or a temporary graft 
(allograft or xenograft) or a tissue engineered substitute such as Integra®). The use of a tissue engineered 
substitute/matrix or temporary graft is generally followed by an autologous skin graft. Maturation of the 
graft may take several weeks and, depending on the severity and location of wound and the degree of 
meshing required for a STSG, the cosmetic outcome is often unsatisfactory. In addition, complications 
such as infection or contractures may occur, which can result in further treatments and procedures, as 
well as prolongation of healing. Furthermore, in the event of a catastrophic event, the current systems 
may be overwhelmed in the ability to handle substantial numbers of burn cases, which is compounded by 
the prolonged nature of healing with current techniques and the high level of expertise required to limit 
complications and increase the likelihood of a satisfactory functional and aesthetic result. Overall, there 
is a growing need to develop improved techniques in acute burn management1. 
Adipose Derived Regenerative Cells (ADRCs) are of emerging interest in the application of wound 
healing. Cells obtained from adipose tissue have been shown to inhibit inflammation2-5 , promote 
angiogenesis5-7, 7-13, stimulate recruitment of endogenous regenerative cells14, 15 and promote salvage of 
damaged cells2, 5, 16. On the basis of these properties, several preclinical studies have been performed 
using freshly isolated and cultured adipose-derived cells in a number of animal models of normal and 
impaired wound healing. The data consistently show improvement of epithelialization and wound healing. 
ADRCs are an advantageous resource because they can be found in abundant quantities, they can be 
harvested with a minimally invasive procedure17, 18, and they can be safely and effectively transplanted 
into an autologous host. 
2.2 
Pre-Clinical Data 
A large number of studies in the literature have described the ability of freshly isolated adipose cells and 
cultured adipose stem cells to improve healing in several small and large animal preclinical models of 
cutaneous wound healing including normal animals, diabetic mice, irradiated skin, mitomycin-treated 
wounds, and ultraviolet-treated skin14, 19, 20. All investigators report improved wound healing parameters 
including increased wound closure rate, increased granulation tissue, and improved wound vascularity and 
perfusion. 
Pre-clinical testing (animal and biocompatibility) of ADRCs and the Celution® System has demonstrated 
safety and biocompatibility across numerous animal models of human disease.   Data with intravenous12, 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 13 of 48 
Date: 
May 14, 2018 
subcutaneous or topical (spray)4 administration show efficacy of ADRCs over a control group treated with 
vehicle alone (lactated Ringer’s solution). Intravenous administration has the advantage of administration 
not having to be available at the time of grafting (i.e. can be delivered following completion of the 
surgical procedure) and potentially may treat more wounds via systemic delivery relative to only treating 
selected wounds via topical delivery. Complete pre-clinical animal and biocompatibility data are provided 
in the Celution® System Investigator’s Brochure.  
2.3 
Clinical Data 
The Celution® System is approved for use as a medical device in the European Union. Hundreds of 
patients have been treated with autologous ADRCs prepared using the Celution® System. These patients 
range in clinical indication from cardiovascular disease to soft tissue reconstruction following breast 
cancer therapy.  
The RESTORE-2 study was a Phase IV (post-market) study evaluating safety and efficacy of ADRC-
enriched fat transplantation in the treatment of subjects with breast deformities post segmental breast 
resection (lumpectomy) with or without radiation therapy. This prospective, single-arm, open-label, multi-
center study enrolled 71 subjects with defects ranging from 25-150 mL at 7 European clinical centers. A 
minimum of 270 mL of adipose tissue were harvested by tissue aspiration. The efficacy data demonstrated 
high degrees of patient (75%) and investigator (85%) satisfaction following ADRC-enriched fat grafting 
to treat breast defects post-breast conservation therapy. The procedure was also shown to be safe and well 
tolerated. RESTORE-2 results provide evidence of safety and efficacy following ADRC delivery for 
subcutaneous soft tissue indications. 
PRECISE was a prospective, double-blind, randomized, parallel group, placebo-controlled, sequential 
dose escalation study that evaluated the safety and feasibility of intramyocardial administration of ADRCs 
in subjects with chronic myocardial ischemia not amenable to revascularization. Following baseline 
electromechanical mapping, subjects received ≤ 15 intramyocardial injections of ADRCs (n=21; median 
dose of ADRCs 42 x 106 per subject) or placebo (n=6: indistinguishable solution) in the area(s) of the 
heart with inducible ischemia. ADRCs were processed using the Cytori Celution® System. ADRC-treated 
subjects demonstrated improvement in maximum oxygen consumption relative to the control group. 
Adverse events and serious adverse events were equally distributed across all treatments groups. 
The APOLLO Clinical Trial was a safety and feasibility study of ADRCs processed by the Celution® 
System and delivered via the intracoronary (IC) route in the treatment of subjects with ST-segment 
elevation myocardial infarction. This was a prospective, double-blind, 3:1 randomized (ADRC: Placebo), 
parallel group, placebo-controlled trial. A total of 14 subjects were enrolled and treated according to 
protocol, 10 subjects received ADRCs and four received placebo. The APOLLO study demonstrated that 
harvest of adipose for the purpose of processing and returning autologous ADRCs via the intracoronary 
infusion of 20 x 106 ADRCs is a safe and practical procedure. ADRC–treated subjects following acute 
myocardial infarction yielded several promising efficacy signals including a > 50% reduction in infarct 
size by MRI compared to placebo treatment.  
The ADVANCE clinical study (NCT01216995) is a safety and efficacy randomized (2:1), 2-arm, 
placebo-controlled, double-blinded clinical study in patients with ST elevation acute myocardial 
infarction. The ADRCs were injected via the intracoronary route at a dose of 20 x 106± 10% or placebo. A 
total of 23 patients were enrolled, with 13 patients receiving ADRCs and 6 receiving placebo, with 4 
subjects not analyzed. While the ADVANCE study did not demonstrate a therapeutic benefit for ADRCs 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 14 of 48 
Date: 
May 14, 2018 
treatment in patients after STEMI other than a possible preservation on LV mass, the ADVANCE study 
did demonstrate intracoronary injection of ADRCs obtained via liposuction was well tolerated, with no 
test material- or injection procedure-related adverse events reported, and was not associated with an 
increased risk of Major Adverse Cardiac and Cerebrovascular Events (MACCEs). 
The ATHENA trials are two ongoing prospective, double-blind, 2:1 randomized (ADRC: Placebo), 
placebo controlled trials in the United States investigating the safety and efficacy of ADRCs in subjects 
with heart failure due to ischemic heart disease. ADRCs (low or high dose) are administered directly into 
the myocardium during a left heart catheterization procedure via 15 injections. A total of 31 subjects were 
randomized prior to termination of enrollment. Tissue harvest in compromised cardiac subjects was 
demonstrated to be feasible and can be performed with an acceptable safety profile. One-year follow-up 
has indicated an improvement in health related quality of life with ADRCs relative to placebo; however, 
no physiologic changes through echocardiogram or SPECT testing were observed21. 
The ACT OA trial is an ongoing double-blind 2:1 randomized placebo controlled trial investigating the 
safety and feasibility of intra-articular injection of ADRCs in the treatment of osteoarthritis of the knee. 
The study completed enrollment of 94 subjects in June 2015. All subjects have completed the study. 
There have been no UADEs. Tissue harvest was demonstrated to be feasible and safe in all enrolled 
subjects. 
The STAR trial is a phase III a double-blind placebo controlled study evaluating subcutaneous treatment 
with ADRCs for hand dysfunction resulting from scleroderma. The trial is enrolled with 88 subjects as of 
June 2016. No related unanticipated adverse events have been reported. The tissue harvest procedures and 
cell injections have been well tolerated without complications. 
A summary of pre-clinical and clinical experience is provided in the Celution® System Investigator’s 
Brochure. 
3 
RATIONALE 
Patients with thermal wounds often require intensive management and have the risk of incomplete wound 
closure, prolonged period to wound closure, dysfunctional tissue healing (i.e. contractures, keloids) and 
infection. Such injuries may ultimately lead to chronic pain and disability. For digits and limbs, 
progressive injury may result in amputation. In addition, more rapid and complete wound healing 
following acute burns could reduce other complications and decrease the time spent in specialized 
hospital units. Cells present within the subject’s own adipose tissue, ADRCs have the potential to improve 
healing following thermal injury by potentially reducing inflammation, improving restoration of blood 
flow, and stimulating local repair cells. Preclinical studies performed by Cytori in a full thickness thermal 
injury porcine model have demonstrated local and systemic delivery of autologous ADRCs without a 
scaffold increase wound re-epithelialization4, 12. Using a similar model but with Integra® skin substitute, 
local delivery of ADRCs is associated with improved wound tissue vascularity and maturation11. In 
previous clinical studies, these cells have a favorable safety profile in acute myocardial injury, heart 
muscle damage, breast deformity following lumpectomy, and OA of the knee.  
4 
STUDY DESIGN 
4.1 
Study Overview 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 15 of 48 
Date: 
May 14, 2018 
The RELIEF Trial is a prospective, open-label, parallel group, usual care controlled, multi-center 
randomized (2:1, active: usual care alone) safety and feasibility study targeting thermal burns. Subjects 
will have at least one deep partial or full thickness burn wounds of > 250 cm2 that is to be autografted 
with a meshed split thickness skin graft (STSG). Subjects randomized to ADRCs will undergo small 
volume fat harvest (100 to 150 mL) performed at initiation of general anesthesia for scheduled burn 
surgery followed by intravenous delivery of ADRCs within 4 hours following completion of Celution 
processing. The lipoaspirate will be processed in the Celution® System to isolate and concentrate ADRCs. 
Following informed consent and initial screening assessments, eligible subjects will undergo pre-
operative testing. On the procedure day, subjects will be randomized to ADRCs (with usual care) or usual 
care alone. Low volume lipoharvest will only be performed on subjects randomized to ADRCs in order to 
obtain 100-150 mL lipoaspirate, which will then be transferred to the Celution®  System for processing to 
isolate and concentrate ADRCs for same-day administration. All treatment will be delivered in a total 
volume of 10 mL which will be delivered by slow intravenous administration into a peripheral vein. 
Following surgery, subjects will be evaluated at time of first dressing change, day 10 (±2) (only if wound 
dressing change planned) and weeks 2 (±3 days), 3 (±3 days), 4 (±3 days), 8 (±7 days), 12 (±14 days), 26 
(±14 days), and 52(±21 days). 
All subjects will undergo digital photography of the wounds, clinical evaluations, microbiology and 
laboratory testing prior to and after the procedure as outlined in Section 9.0, Study Visit Requirements, and 
in the Schedule of Procedures (Appendix A).  
The 1st 5 subjects enrolled in active treatment will be observed for adverse events over a 7 day period. If 
no SAEs occur during that period, for that individual subject, the next subject enrolled in active treatment 
may be entered with the same 7 day observation period. The safety results of the first 5 subjects will be 
reviewed by the DMC and their evaluation will be used in conjunction with the clinical data collected to 
date, and if appropriate, to potentially remove the staggering approach to the study. Enrollment after the 
first 5 subjects may continue only after the DMC has completed its safety review and recommends 
continuation. 
4.2 
Study Population 
The study population will include subjects with a 20% - 50% TBSA and at least one deep partial or full 
thickness burn wound with an area of  ≥ 250 cm2  who will undergo an escharectomy and a planned 
autologous meshed STSG to the identified area(s).   
The rationale for including subjects with TBSA of 20-50% is that these subjects often have meshed 
STSG, increasing their risk of wound contraction and scarring. Thus, they could benefit from ADRCs as 
an adjunctive therapy with the potential for enhancing the engraftment and healing process. These 
subjects, those between 20% - 50%, also tend to be more hemodynamically stable in that their fluid 
requirements are less than those with greater wound size area. This relative clinical stability earlier in 
their initial treatment phase may allow them to better tolerate the lipoaspiration procedure which serves as 
the source for the ADRCs.  
4.3 
Sample Size 
Up to a total of 15 subjects will be enrolled. Each patient may contribute up to three qualified wound 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 16 of 48 
Date: 
May 14, 2018 
areas for the analysis. If more than one wound is identified, each must be noncontiguous with the other(s). 
Therefore, between 15 and 45 wounds will be evaluated. Wound areas that have been treated with a 
biologic dressing such as Alloderm® or Integra® are not qualified for analysis. However, a wound area 
that receives excision and grafting as described in this protocol without the application of a biologic 
dressing may be qualified even if other wound areas in the subject are not qualified because they have 
been treated with a biologic dressing.  
4.4 
Clinical Sites 
Considering the patient population is expected to have an overall large %TBSA, based on the general 
prevalence of the this type of burn injuries in the US population, up to ten (10) regional burn centers 
within the United States will be selected to participate in the RELIEF Trial. 
4.5 
Study Duration 
Enrollment is anticipated to be completed over 18 months. For each patient, the study duration will 
include a 12 month follow-up period. The total duration of the RELIEF Trial is estimated to be 30 
months. 
4.6 
Study Endpoints 
4.6.1 Primary Endpoints 
 Safety and Feasibility 
Safety will be evaluated based on the incidence, type and seriousness of adverse events related to the IV 
administration of test substance as well as the low volume lipoharvest procedure. Adverse events will be 
assessed according to the NIH Common Terminology Criteria for Adverse Events (CTCAE) v4.0 for 
scale grading adverse events. 
Microbiological testing (culture and sensitivity) will be performed on the ADRC treatment dose produced 
and administered on site. 
Feasibility will be determined as the ability to obtain > 100 mL adipose tissue, obtain ≥ 20 x 106 ADRCs, 
and deliver the prepared cell dose. 
 
4.6.2 Key Secondary Endpoints 
 Percent epithelialization of the graft at time of first dressing change and day 10 (only if wound 
dressing change planned) and weeks 2, 3 and 4 
 Percent take of the graft at time of first dressing change and day 10 (only if wound dressing 
change planned) and weeks 2, 3 and 4  
Digital photography will be performed at surgery and at each follow-up visit for blinded independent 
review.  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 17 of 48 
Date: 
May 14, 2018 
Graft take will be assessed as the area over which vascularization is evident and sufficient anchorage to 
the underlying tissue exists to support epidermal growth. Take will be expressed as a percentage of the 
area originally covered by the graft. Percent take should be estimated separately for each graft-treated site. 
Both of the above endpoints will be evaluated by (a) visual inspection by the treating surgeon, and (b) 
standardized digital photography and scoring centrally by a blinded trained assessor.  
 Percent of group with complete wound closure at each assessment through to 12 weeks  
4.6.3 Exploratory Endpoints 
 Transepithelial water loss at weeks 2, 3 and 4  
 Wound pain VAS at time of first dressing change and day 10 and weeks 2, 3 and 4  
 Pruritis VAS at weeks 3, 4, 8, 12, 26 and 52  
 Patient and Observer Scar Assessment Scale (v2.0) weeks 3, 4, 8, 12, 26 and 52 
 Skin elasticity (Delfin Elastimeter) measurement at 12, 26 and 52 weeks 
 Vancouver Scar Scale at 12, 26 and 52 weeks 
 Skin pigmentation (Delfin SkinColorCatch) measurement at weeks 12, 26, and 52 
 Skin hardness (Delfin Skin Fibrometer measurement) at weeks 12, 26, and 52 
 Biomarkers related to burn injury22 (such as C-reactive protein (CRP), IL-6, IL8, IL1β, 
interleukin-1 receptor antagonist (IL-1ra); neutrophil gelatinase-associated lipocalin (NGAL); 
Tumor Necrosis Factor-α (TNFα),  and tumor necrosis factor receptor 1a (TNFR-1a)) and 
related to scarring23, 24 (such as  amino-terminal propeptide of type III procollagen, (PIIINP), 
TIMP1, MMP2, MMP9 and VEGF-A) will be collected at baseline (prior to treatment), days 
6, and 10 and weeks 2, 3, 4, 8 and 12 post ADRC administration. Serum sample will be 
collected from 4 to 5 ml of whole blood that is centrifuged, separated into 500-µL aliquots, 
and stored at  -80°C at the clinical site serum bank or central lab until use.  
 Serum biomarkers will be measured using commercial Enzyme-Linked ImmunoSorbent Assay 
(ELISA).  
4.7 
Inclusion and Exclusion Criteria 
4.7.1 Inclusion Criteria 
Subjects will be enrolled into this study only if they meet ALL of the following criteria: 
1. Males or females, ≥ 18 to ≤ 65 years of age 
2. BMI > 20 kg/m2 
3. Burn TBSA 20% - 50% 
4. At least one deep partial thickness and/or full thickness thermal burn ≥ 250 cm2 on the arms, legs, 
back, abdomen or chest that is anticipated to be covered with a meshed autologous STSG and that 
has not been treated previously with a biologic dressing such as Alloderm® or Integra® 
5. Ability to safely undergo adipose tissue harvest procedure that is anticipated to yield ≥ 150 mL of 
adipose tissue at a site that is free from infection 
6. Donor site availability for skin graft harvest 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 18 of 48 
Date: 
May 14, 2018 
7. Able to provide written informed consent, signed by either the patient or their legally authorized 
representative 
8. Women and men of child-bearing potential agreeing to use contraception during the study. 
Acceptable methods include surgical sterility, IUDs, hormonal contraception or double barrier 
methods. 
4.7.2  Exclusion Criteria 
Subjects will not be enrolled into this study if they meet ANY of the following criteria: 
1. Burn > third degree (i.e. involvement of deeper tissues, such as muscle, tendon, or bone) 
2.  Subjects with electrical or chemical burns 
3. Subjects with significant inhalation injuries necessitating intubation and mechanical ventilation or 
requiring > 50% FI02 on a continuous basis to maintain oxygenation (02 sat > 90%) 
4. In the opinion of treating physician, patient not to expected to survive beyond 30 days 
5. Pre-existing condition requiring current use of immunosuppressive medication or systemic 
steroids 
6. Pregnant or lactating. Pregnancy as determined by a positive pregnancy test at screening or 
baseline 
7. Known history of HIV infection, or has active Hepatitis B or active Hepatitis C infection. 
8. Cancer requiring chemotherapy or radiation within previous 6 months or resection within the last 
5 years (other than basal cell carcinoma) 
9. Known chronic renal failure (serum creatinine > 2 mg/dL) or chronic liver disease  
10. Pre-existing medical conditions that would interfere with wound healing (i.e., diabetic patients 
with Hemoglobin A1c ≥8.0%, malignancy, autoimmune disease) 
11. Subjects with psychiatric conditions that are anticipated to result in protocol noncompliance 
12. Chronic illicit drug or alcohol use that is anticipated to interfere with patient compliance to the 
protocol 
13. Participation in another clinical trial within 60 days of screening visit 
14. Any concurrent disease or condition that, in the opinion of the investigator, would make the 
patient unsuitable for participation in the study 
5 
ENROLLMENT 
5.1 
Subject Enrollment 
Subjects are considered enrolled in this study when all of the following have occurred: 
1. Written informed consent is obtained  
2. All inclusion criteria and no exclusion criteria have been met 
3. All screening evaluations are complete 
4. Commencement of fat harvest (except for usual care control subjects who will not undergo a 
lipoaspirate procedure) 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 19 of 48 
Date: 
May 14, 2018 
 
5.2 
Randomization and Subject Identification 
Randomization to ADRC and usual care will occur within 2 hours prior to the scheduled surgery for 
STSG.   
Randomization will be done via an interactive web response system (IWRS). Subjects will be randomized 
in a 2:1 ratio to receive intravenous delivery of either Celution®  System processed ADRCs with usual 
care or to usual care alone.  
A total of up to 15 subjects will be enrolled. Each patient will contribute up to three qualified wound areas 
for the analysis. If more than one wound is identified, each must be noncontiguous with the other(s). 
Therefore, between 15 and 45 wounds will be evaluated. 
The 1st 5 subjects enrolled in active treatment will be observed for adverse events over a 7 day period. If 
no SAEs occur during that period, for that individual subject, the next subject enrolled in active treatment 
may be entered with the same 7 day observation period. The safety results of the first 5 subjects will be 
reviewed by the DMC and their evaluation will be used in conjunction with the clinical data collected to 
date, and if appropriate, to potentially remove the staggering approach to the study. Enrollment after the 
first 5 subjects enrolled in active treatment may continue only after the DMC has completed its safety 
review and recommends continuation. 
5.3 
Stopping Rules 
The study will be stopped and patient enrollment will be suspended if any of the following events occur: 
1. Acute cardiovascular adverse event occurring within seventy-two (72) hours of the ADRC 
infusion. 
2. Acute allergic or anaphylactic response within seventy-two (72) hours of the ADRC infusion. 
3. Acute pulmonary adverse events such as acute respiratory distress syndrome (ARDS) and renal 
adverse events such as acute renal failure (ARF) within  seventy-two (72) hours of the ADRC 
infusion.  
The Sponsor will notify the DMC and FDA immediately for their review and recommendation on study 
continuation.   
5.4 
Blinding Procedures and Safeguards 
The “blinded party” (photographic assessor(s) with no knowledge of the subjects treatment assignment) 
are those involved in the independent evaluation of the wound digital photographs. 
All others involved in the study are considered the “unblinded parties”, meaning those that will or may 
have knowledge of a patient’s treatment assignment. 
5.5 
Subject Withdrawal and Replacement 
Subjects may withdraw from the study at any time and for any reason without penalty or prejudice to his 
or her future medical care. If a subject is prematurely withdrawn from the study for any reason, the 
reason(s) for withdrawal must be recorded in the Subject’s source documentation and on the eCRF.  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 20 of 48 
Date: 
May 14, 2018 
The Investigator must make every effort to perform the Early Termination evaluations. This visit shall 
take place as soon as possible after it is determined that the Subject will be withdrawn from the study and 
will comprise the observations and procedures scheduled at the next visit. 
6 
CELUTION® SYSTEM 
6.1 
Celution® System Description 
The Celution® System consists of a stand-alone re-useable hardware unit called the Celution® 800/IV 
Device with v5.1 firmware with Heater Attachment accessory, the Celution® 805/IV Consumable Set, 
Celase® and Intravase®. The Celution® System prepares an ADRC output from adipose tissue collected by 
standard syringe aspiration techniques. The tumescent fluid is composed of: 500 mL of lactated Ringers 
solution, 20 mL of 1% lidocaine, and 1mg of epinephrine.  
Following the collection and preparation of tissue via fat harvest, the adipose tissue is introduced into the 
device’s collection canister in order to wash the adipose tissue and remove deleterious substances (such as 
cellular debris) (Detailed instructions for use are found in the Celution®  User Manual). 
6.2 
Device Characterization and Intended Use 
The Celution® 800/IV Device is intended to be used in conjunction with the Celution® 805/IV 
Consumable Set, Celase and Intravase to digest human adipose tissue in order to further extract, wash, 
and concentrate adipose derived regenerative cells intended for autologous reinfusion (intravenous) for 
burn wounds for investigational use in the RELIEF  clinical trial.  
6.3 
Contraindications 
1. Non-autologous use  
2. Use of any tissues other than adipose  
6.4 
Intended Clinical Performance 
The Celution® System is designed to process lipoaspirated tissue to separate ADRCs from adipose tissue 
by enzymatic disassociation of the tissue and using buoyancy differences and centrifugation to separate 
and then concentrate the ADRCs from lipid containing adipocytes. When ADRCs are prepared using the 
Celution® System, the resultant cell suspension contains all of the components naturally occurring in the 
native tissue. Preparation of autologous ADRCs for delivery using the Celution® System involves no cell 
culture. The prepared ADRC dose can be administered to the same patient within four hours.  
A percentage viability of > 70% of the ADRC output will be used as the acceptance criteria. 
The total viable cell count will be performed using a validated system that counts both viable and non-
viable nucleated cells (NucleoCounter NC-100® Automated Cell Counting System). This count is used to 
calculate the total number of live nucleated cells from the entire preparation, to arrive at a quantity of 
viable cells for treatment of the patient. 
6.5 
Celution® System Output: Physical, Chemical, and Mechanism of Action 
The product of the Celution® System is an ADRC output obtained from autologous lipoaspirate. The 
suspension of viable ADRCs has been characterized with a average viability of >70% and the average 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 21 of 48 
Date: 
May 14, 2018 
yield is 3.22 x 105 ± 1.48 cells per gram of adipose tissue processed in the Celution®  System. An index of 
regenerative cell potential, the CFU-F assay, shows that 1.51% of those ADRCs form colonies (mean 
range of 0.13 to 4.08% colony forming units).  
The product is a suspension of cells in a diluent. The cellular components of the suspension are made up 
of nucleated and non-nucleated cells. The non-nucleated cells are red blood cells (RBC) that comprise > 
95% of the total cell suspension. The nucleated cells make up approximately 0.1 – 5% of the total cell 
suspension.  
The combination of these four phenotypes will account for approximately 90% of nucleated cells in the 
product. Table 1 summarizes the ADRC cellular suspension processed by the Celution® System.  
Table 1. ADRC cellular suspension components and concentrations  
Cell Type 
Phenotype 
Relative Identity of Nucleated 
Cell Population 
Non-nucleated Cells 
Red Blood Cells 
 
Endothelial Cells 
CD45-, CD31+, CD34+ 
> 2% 
Stromal Cells 
CD34+, CD31-, CD45- 
> 5% 
Leukocytes 
CD45+, CD31-, CD34- 
> 5% 
Mural Cells 
CD45-, CD34-, CD 31- ,CD146+ 
> 2% 
 
6.6 
Proposed Mechanism of Action of ADRCs 
The proposed mechanism of action of the ADRCs prepared with the Celution® System is postulated to be 
modulation of inflammation, promotion of angiogenesis and prevention of cell apoptosis. Studies suggest 
that ADRC therapy changes the inflammatory response and augments the regenerative response starting 
early in the injury process2-4, 8, 11, 12. Studies have detected significant amounts of paracrine growth 
factors, which have been shown to facilitate vascularization, and factors associated with anti-
inflammatory effects, thereby ameliorating injury by pro-inflammatory cytokines8. This has been 
demonstrated to repair healing impaired, deep, and chronic wounds8, 9, 25-27. Viability characterization of 
ADRCs as described above, in addition to pre-clinical animal data from Cytori and other published 
reports, support this hypothesis. 
7 
STUDY TREATMENTS 
Subjects randomized to ADRCs will receive active treatment (intravenous infusion of 20 × 106 ADRCs 
into a peripheral vein). Subjects randomized to the control group will not undergo fat harvest and not 
receive any study treatment. All subjects will continue their usual care treatment. 
7.1 
Product Description - ADRCs 
Lipoaspirate will be obtained through a low volume lipoharvest (100-150 mL) which will be performed at 
the start of general anesthesia for the scheduled burn surgery. The lipoaspirate will be processed using the 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 22 of 48 
Date: 
May 14, 2018 
Celution® System to produce ADRCs. The ADRCs will be delivered via intravenous approximately 
within 4 hours of Celution processing.  
The adipose tissue is introduced into the device’s collection container in order to wash and process the 
tissue. Based on a fat harvest of 100-150 mL, the expected cell output would be approximately 20 to 40 
million cells. The target dose for the study is 20 million cells. 
The excipients in the cell suspension are composed of residual Celution® System reagents and diluent. 
Specifically, the residual reagents are collagenase (<0.005 Wünch Units/mL) and DNase (<100 Kunitz 
Units/mL). The diluent is Lactated Ringers solution (USP).  
Adipose tissue processing is detailed in the Celution®  System Users Manual. Preparation of the active 
study treatment is provided in the Study Reference Manual. 
7.1.1 Treatment Dose Control 
ADRC count and viability will be determined using a validated system that counts both viable and non-
viable nucleated cells (NC-100 NucleoCounter® Automated Cell Counting System, Enfield, Connecticut, 
USA) using the following criteria: 
 Nominal cell count:  20 x106 ADRCs  
 A minimum cell count within 15% of the nominal cell count is required (i.e., a dose as low as 17 × 
106 ADRCs is acceptable if 20 × 106 ADRCs is not available) 
 Cell viability: ≥ 70% 
 If cell viability is < 70%, as determined by the NucleoCounter® Automated Cell Counting System, 
the subject will not be treated but will be followed per study protocol for safety.  
 Negative result in Gram stain testing (see Section 7.2) 
 If the Gram stain testing result is positive, the subject will not be treated but will be followed per 
study protocol for safety. 
 
7.2 
Study Treatment Sterility Testing 
Following cell processing in the Celution System sterility testing will be performed as described below 
and more fully in the Study Reference Manual and the Cell Preparation Manual.  
A negative Gram stain test result is required prior to injections of ADRCs. If the sample is determined to 
be positive for bacteria then the subject should not receive any study treatment, but will be followed per 
study protocol for safety. 
Further testing (aerobic bacteria culture (e.g. BacT Alert or BacTec)) will be performed in order to test for 
the presence of any low level microbial contamination that might not be apparent in the gram stain test. 
Should a culture be deemed positive for microbial activity, the investigator will be immediately notified. 
The study patient will be evaluated and a course of treatment and/or antibiotics may be administered, as 
determined by the study investigator. The source of the contamination will be evaluated as appropriate. If 
the culture test indicates potential bacterial contamination of the study treatment and the clinical follow up 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 23 of 48 
Date: 
May 14, 2018 
indicates potential or actual infection of the subject, the FDA and IRB will be notified within 15 days of 
the Sponsor being made aware of any positive test results. 
The following flow chart describes the activities associated with positive or negative outcomes in these 
two tests of sample sterility.  
 
Figure 1: Sterility Testing of ADRC Samples 
 
7.3 
 ADRC Characterization 
Additional ADRC phenotypic characterization beyond the cell counting and bacterial testing required for 
dose preparation may be performed for subjects for whom ADRCs in excess of the number needed for 
dosing, cell counting, and bacterial testing are available. Such testing should be performed according to 
methods developed by Cytori. Flow cytometry methods will be used to determine ADRC cellular 
composition28. Particularly, detailed characterization will be performed on left over cells once the cell 
dose preparation has been prepared for the injection procedure. Within the ADRC population, cells will 
be identified phenotypically by combination of the following markers: CD45, CD34, CD31 and CD146. 
Once the cell dose is prepared according to criteria described in Section 7.1.1, any excess ADRCs may be 
stained and fixed at the clinical site using antibodies directed to CD31, CD34, CD146 and CD45 proteins 
according to instructions in the Study Reference Manual (Cytori Work Instruction). Samples will be then 
shipped to the testing facility within 92 hours.  
Based on the expression of these four markers, the major populations will be defined as follow: 
Leukocytes 
CD45+ 
Endothelial Cells 
CD34+/CD31+/CD45- 
Stromal Cells 
CD34+/CD31-/CD45- 
Mural cells 
CD34-/CD31-/CD45-/CD146+ 
Other markers (such as CD206, CD14, CD90, CD73, CD105 and CD44 or other related markers) may be 
used to further characterize ADRCs subpopulation. 
Gram Stain 
Positive 
DO NOT 
ADMINISTER 
ADRC 
Aerobic 
Culture 
Negative 
No Further 
Action 
Positive 
Notify IRB and 
FDA 
Negative 
ADMINISTER 
ADRC 
Aerobic 
Culture 
Negative 
No Further 
Action 
Positive 
Investigator 
Notification  
Notify IRB and 
FDA 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 24 of 48 
Date: 
May 14, 2018 
8 
STUDY ASSESSMENTS 
All parameters will be conducted at specific time points as outlined in this section. As a reference point 
during the study, a Schedule of Procedures is provided in Appendix A. 
8.1 
Medical History, Physical Examination & Vital Signs 
A complete medical history will be collected at Screening and will include demographic information, 
current and past medical conditions and a summary of the burn event. Any adverse event that occurs after 
the ICF is signed and prior to the fat harvest is to be recorded as an update to the Medical History. 
Physical examinations should be based on the following body systems: general appearance, head (ear, 
eyes, nose and throat), respiratory, abdomen, musculoskeletal, neurological, and skin, including total burn 
surface area (TBSA) on admission, percent of third degree burns, and other trauma related to the burn 
event. Vital signs to be obtained include the following: 
 Blood pressure (systolic and diastolic; mm/Hg) 
 Heart rate (beats per minute) 
 Body temperature (°C) 
 Respiration rate (per minute) 
 
8.2 
Adverse Events 
Adverse events will be assessed throughout the study according to the NIH Common Terminology 
Criteria for Adverse Events (CTCAE) v4.0 for scale grading adverse events. 
8.3 
Burn Evaluations 
The physical characteristics of the selected burn areas and the graft (up to 3 per subject) as well as the 
subjective evaluation of symptoms will be evaluated using several assessment tools. The assessment tools 
are listed below and detailed information and instructions provided in the Study Reference Manual. 
Planned study days are listed below but an acceptable range of days (±) is in the schedule of events. 
 Percent epithelialization at early dressing changes (estimated time of first dressing change and day 
10 after graft application and at weeks 2, 3 and 4 (by surgeon evaluation and blinded independent 
review of standardized photographs)  
 Percent take of the graft at early dressing changes (estimated time of first dressing change and day 
10 after graft application (if wound dressing must be changed) and at weeks 2, 3 and 4 
 Occurrence of complete wound healing at each assessment weeks 4 to 12 
 Transepithelial water loss at weeks 2, 3 and 4 
 Wound pain VAS at time of first dressing change and day 10 and weeks 2, 3 and 4 
 Pruritis VAS at 3, 4, 8, 12, 26 and 52 weeks  
 Patient and Observer Scar Assessment Scale (POSAS) at 3, 4, 8, 12, 26 and 52 weeks 
 Vancouver Scar Scale at 12, 26, and 52 weeks 
 Skin elasticity measurement at 12, 26 and 52 weeks (Delfin SkinElastimeter) 
 Skin pigmentation (Delfin SkinColorCatch) measurement at weeks 12, 26, and 52 
 Skin hardness (Delfin SkinFibrometer) measurement at weeks 12, 26, and 52 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 25 of 48 
Date: 
May 14, 2018 
 Percent of wounds with complete wound closure at weeks 2, 4, 8 and 12 
 Digital photography of treated wounds on day 1 and each follow up visit 
 Biomarkers related to burn injury will be assessed from 4-5mL blood (serum) samples drawn at 
baseline (prior to treatment), time of first dressing change and day 10 and weeks 2, 3, 4, 8 and 12 
post-ADRC administration.  
8.4 
Prior and Concomitant Medications 
Any medication a subject receives is considered a concomitant medication, and must be recorded in the 
subject’s source documentation throughout the study. All concomitant medications will be recorded in the 
eCRF starting at screening through the 52 week visit. Information to be recorded on the eCRF will 
include: generic medication name, route of administration, dosage, indication, start date, and stop date.  
Medications used as part of the tissue harvest procedure and the escharectomy/grafting surgeries do not 
need to be recorded in the eCRF but should be recorded as part of the operative records.  
8.4.1 Prohibited Medications 
Subjects should not receive the following medications for the duration of the study: 
 Any other investigational drug or agent 
 Any chemotherapy or immunosuppressive medication 
 Systemic steroids exceeding prednisone 10 mg daily (or equivalent) for periods exceeding 4 weeks 
 Any anticoagulant administered for systemic anticoagulation that would contraindicate a 
lipoaspiration procedure. Subcutaneous heparin or low molecular weight heparin for deep vein 
thrombosis prophylaxis is acceptable  
 A substantial anticoagulant such as a Glycoprotein IIb/IIIa inhibitor/anti-platelet class drug was 
administered within 2 weeks prior to fat harvest (such as ReoPro, Integrilin or Aggrastat) 
If treatment with any prohibited medication becomes necessary during study participation, the subject will 
be followed; however, the subject would not be included in the PTE population. 
8.5 
Laboratory Procedures 
All laboratory assessments will be performed locally at each center’s laboratory by means of their 
established methods (using site specific laboratory normal values). Blood samples should be taken using 
standard venipuncture techniques according to the laboratory guidelines. The approximate total blood 
volume that will be taken for the laboratory and biomarker assessments will be 50 to 60 mL. 
8.6 
STUDY VISIT REQUIREMENTS 
The Schedule of Procedures is outlined in Appendix A. 
8.6.1 Day -2 to Day -1: Screening  
Within 48 hours prior to scheduled excision and STSG surgery, subjects will undergo the following 
screening assessments: 
 Written informed consent from the patient or their legally authorized representative  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 26 of 48 
Date: 
May 14, 2018 
 Age, gender, height and weight 
 Inclusion and exclusion criteria evaluation  
 Medical history 
 Concomitant medications 
 Physical examination  
 Vital signs 
 Biomarkers 
 Laboratory tests  
o CBC with platelets 
o INR, PTT 
o Electrolytes, alkaline phosphatase, AST, ALT, bilirubin, total protein, albumin, BUN, 
creatinine, and, for patients with diabetes only, evaluation of HbA1c levels 
o Blood draw (4-5mL) to obtain serum for subsequent testing for burn biomarkers  
 Pregnancy test for female subjects 
 Evaluation of suitability and probable body location for fat harvest by the surgical specialist who 
will perform the lipoaspirate procedure  
Enrollment will occur by a designated staff following confirmation by the treating surgeon that the patient 
is to proceed with a skin graft from the patient’s donor site.  Enrollment will occur within 2 hours of the 
scheduled procedure.  
8.7 
Procedure Day (Day 1)  
The following assessments are to be conducted: 
 For All Subjects 
o Randomization 
o Vital signs 
o Assessment for adverse events 
o Digital photography of wounds 
o Laboratory tests  
 CBC with platelets 
 INR, PTT 
 Electrolytes, alkaline phosphatase, AST, ALT, bilirubin, total protein, albumin, 
BUN, creatinine 
 
 For Subjects Randomized to Treatment Arm only 
o Low volume fat harvest 
o Microbiology testing of dose samples (ADRCs) at baseline (prior to ADRCs 
administration) 
o ADRC dose preparation and delivery 
8.7.1 Fat Harvest 
8.7.1.1  General Requirements 
 Fat harvest will be performed at the start of general anesthesia for the planned excision and STSG  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 27 of 48 
Date: 
May 14, 2018 
 In order to ensure that surgical resources for standard of care escharectomy are not diverted to the 
fat harvesting procedure, fat harvest will be performed by a qualified surgeon not otherwise 
involved in the burn surgery at that time. 
 Standard tissue calipers or expert surgical specialist examination should be used to assess possible 
body sites for subcutaneous fat tissue. Any subject with an active skin infection at the site of 
lipoharvest will be excluded from the study 
 Fat harvest should NOT be performed if an anticoagulant has been administered within 1 hour 
prior, a substantial anticoagulant such as a Glycoprotein IIb/IIIa inhibitor/anti-platelet class drug 
was administered within 2 weeks prior (such as ReoPro, Integrilin or Aggrastat), or if there is an 
abnormally high INR or PTT 
Operative details such as start and stop time, weight of lipoaspirate, dose preparation time will be 
recorded on the appropriate eCRF. 
8.7.1.2  Fat Harvest Procedure: 
A specific set of requirements has been established for the collection of fat that can then be used for the 
successful preparation of ADRCs using the Celution® technology. Therefore, the following conditions 
and procedures are to be used. Additional information will be provided in the Celution® Instructions for 
Use: 
 Syringe-based fat harvest is required 
 A total volume of 100-150 mL of adipose tissue must be harvested 
 Symmetric fat removal is required, keeping the overall area of aspiration as small as possible  
 The abdominal region is the preferred site for fat harvest, however multiple sites should be 
evaluated and prepared and non-abdomen regions (e.g., inner thigh) used if abdomen not available 
 Make an approximately 0.5 cm stab skin incision 
 Infiltrate tumescent solution using a 14 gauge, up to 30 cm, blunt LAMIS™ infiltrator for 
tumescent fluid administration ; tumescent fluid should be infiltrated at a ratio of approximately 
1:1 to 3:1 of tumescent solution to fat to be harvested 
 The tumescent fluid formula to be used is: 
 500 mL of Lactated Ringers solution  
 20-50 mL of 1% Lidocaine 
 1 mg of epinephrine 
 To sufficiently induce vasoconstriction/hemostasis during the tissue harvest procedure a minimum 
of 100 mL of tumescent fluid must be used. Estimated volume should generally be limited to 500 
mL 
 Approximately 10 minutes after the tumescent fluid injection, the adipose tissue is harvested 
through the same incision, using an up to 32 cm long, 3-5 mm inner diameter Toomey cannula 
with a Mercedes standard tip attached to a sterile 60 mL Toomey syringe 
 After the first syringe is filled (complete filling is not required) it is detached from the cannula, 
capped with a sterile cap and set aside; additional syringes are filled until the desired amount of fat 
is harvested  
 Fat harvest will be limited to areas where tumescent fluid has been infiltrated 
 Vital signs are monitored during tissue harvest procedure 
 Close surgical incision as per the surgeon’s standard procedure. Apply pressure bandage 
immediately upon conclusion of tissue harvest 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 28 of 48 
Date: 
May 14, 2018 
 
8.7.1.3 Fat Harvest Stopping Rules 
The physician performing the fat harvest procedure should continuously monitor the patient for signs of 
significant bleeding from the puncture site(s) and overall hemodynamic stability. The tissue harvest 
procedure should be terminated if any of the following occur: 
 Drop in systolic blood pressure < 90 mm/Hg requiring pressor support 
 Profuse or uncontrollable bleeding from the puncture site(s) 
 Rapid expansion of subcutaneous space at the fat cell tissue harvest site(s) related to bleeding into 
the subcutaneous space 
 Hemoperitoneum or pneumopertineum 
 Hemothorax or pneumothorax 
 Evidence of perforation of a vascular structure that requires ligature or surgical control 
 Evidence of perforation into abdominal cavity, peritoneum or gastrointestinal organ 
Should any of the above occur, the fat harvest procedure should be terminated and the patient treated 
according to standard of care. DO NOT PROCEED WITH ADRCs ADMINISTRATION. Complete the 
study specific SAE form and notify the sponsor within 24 hours.  
8.7.2 Digital Photography 
Digital photographs of the target wounds must be taken shortly after application of the STSG. Images of 
wounds will be taken by using the Silhouette Star System in accordance with the detailed work instruction 
provided in the Study Manual. Digital photographs will be taken at a fixed distance of approximately 30 - 
50 cm from the wound. A reference image to identify the location of the target wound(s) with reference to 
anatomical landmarks should also be captured at the time of grafting. Prior to imaging, a label (with date, 
Subject number, and wound identification) and ruler (to indicate the longest length and width) will be 
placed near each wound site (within the camera’s field of view) to track and identify each image. Images 
will be captured from directly above the wound (approximately perpendicular to the center of the wound 
surface) and at an oblique angle (approximately parallel to the center of the wound surface) to show scar 
height above adjacent skin. For the oblique images, a scale will be placed within the frame and 
immediately adjacent to the wound and perpendicular to the scar to allow assessment of scar height. 
8.7.3 ADRCs Delivery 
If subjects become hypotensive and require vasopressors to maintain organ perfusion between the 
collection of lipoaspirate and the intravenous introduction of ADRCs DO NOT PROCEED WITH 
ADRCs ADMINISTRATION. 
 
Sterile technique should be maintained throughout the procedure. The intravenous ADRCs infusion will 
be by administered by peripheral intravenous administration. An intravenous catheter (20 or 22 gauge) 
will be used to administer the ADRCs. The 5 mL output from the Celution System will be diluted to 
achieve 10 mL lactated Ringer’s solution containing 20 x 106 ADRCs in a sterile syringe. The syringe 
will be attached to the sterile macro (part # or designation) syringe filter and the contents of the syringe 
will be injected into the catheter slowly. The catheter will be flushed with 5 mL of lactated Ringer’s 
solution from a separate sterile syringe. 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 29 of 48 
Date: 
May 14, 2018 
8.8 
Post-ADRC Administration time of first dressing change and Day 10 (±2 days)*  
The following assessments are to be conducted: 
 Physical examination 
 Vital signs 
 Assessment for adverse events 
 Concomitant medications  
 Biomarkers 
 Laboratory tests (time of first dressing change only): 
o CBC with Platelets  
o Electrolytes, alkaline phosphatase, AST, ALT, bilirubin, total protein, albumin, BUN, 
creatinine 
 
The following assessments, tests and questionnaires should be conducted in the order listed below (as 
applicable to each visit) and prior to the other listed tests: 
 Percent epithelialization of the graft (surgeon evaluation) 
 Percent take of the graft** 
 Digital photographs of wound with ruler to indicate the longest length and width 
 Wound pain VAS  
 
*Day 10 assessments performed only if wound dressing is being changed between days 8 and 12.  
**Graft take will be assessed as the area over which vascularization is evident and sufficient anchorage to 
the underlying tissue exists to support epidermal growth. Take will be expressed as a percentage of the 
area originally covered by the graft. Percent take is estimated separately for each of the grafted study 
sites. 
 
8.9 
Post-ADRC Administration Follow-up visits:  Weeks 2 (±3 days), 3 (±3 days) and 4 (±3 days)  
The following assessments are to be conducted: 
 Physical examination 
 Vital signs 
 Assessment for adverse events 
 Concomitant medications  
 Biomarkers 
 
The following assessments, tests and questionnaires should be conducted in the order listed below (as 
applicable to each visit): 
 
 Percent epithelialization of the graft  
 Percent take of the graft 
 Transepithelial water loss  
 Digital photographs of wound with ruler to indicate the longest length and width 
 Occurrence of complete wound closure  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 30 of 48 
Date: 
May 14, 2018 
 Wound pain VAS  
 Pruritis VAS at Weeks 3 and 4 
 Patient and Observer Scar Assessment Scale (POSAs) (Weeks 3 and 4 only) 
 
8.10 Post-ADRC Administration Follow-up visits: Weeks 8 (±7 days), 12 (±7 days), 26 (±14 days), 
and 52 (±21 days)  
The following assessments are to be conducted: 
 Physical examination 
 Vital signs 
 Assessment for adverse events 
 Concomitant medications  
 Biomarkers (Weeks 8 and 12 only) 
 
The following assessments, tests and questionnaires should be conducted in the order listed below (as 
applicable to each visit): 
 
 Digital photographs of wound with ruler to indicate the longest length and width 
 Occurrence of complete wound closure (Weeks 8 and 12) 
 Pruritis VAS 
 Patient and Observer Scar Assessment Scale (POSAS)  
 Vancouver Scar Scale  (Weeks 12, 26 and 52 only) 
 Skin elasticity (Delfin SkinElastimeter) measurement (Weeks 12, 26 and 52 only) 
 Skin pigmentation (Delfin SkinColorCatch measurement) at Weeks 12, 26, and 52 
 Skin hardness (Delfin SkinFibrometer measurement) at Weeks 12, 26, and 52 
A summary table of all follow up evaluations is outlined in Appendix A: Schedule of Procedures.  
 
8.11 Early Termination Evaluation 
Subjects that discontinue early from the study, unless consent is withdrawn, shall have an Early 
Termination (ET) evaluation. This visit shall take place as soon as possible after it is determined that the 
Subject will be withdrawn from the study.  
The observations and procedures for the ET evaluation are the same as those required at the Week 52 
visit. 
The reason for early withdrawal must always be clearly documented in the Subject’s source 
documentation. Contact with the Subject must be attempted to determine overall health status, and contact 
details must be documented in the Subject’s source documentation. If lost to follow-up, details of three 
contact attempts followed by a certified letter must be documented in the Subject source documentation.  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 31 of 48 
Date: 
May 14, 2018 
9 
RISK/BENEFIT ANALYSIS 
9.1 
Context of the proposed investigation: 
Wound healing is a complex multifactorial process involving the interaction of inflammation, granulation 
tissue formation, re-epithelialization, and angiogenesis. For deep partial thickness and full thickness 
burns, acute burn management involves multiple activities including protecting the wound from further 
injury, initial cleansing and debridement and determination of dressings with or without a topical 
antimicrobial agent. Fluid resuscitation, prevention of hypothermia and pain management are also critical 
aspects of management. Surgical procedures involve escharectomy with further debridement and 
determination of skin grafting (often autologous split thickness skin graft (STSG) or a temporary graft 
(allograft or xenograft) or a tissue engineered substitute such as Integra®). The use of a tissue engineered 
substitute/matrix or temporary graft is generally followed by an autologous skin graft. Maturation of the 
graft may take several weeks and, depending on the severity and location of wound and the degree of 
meshing required for a STSG, the cosmetic outcome is often unsatisfactory. In addition, complications 
such as infection or contractures may occur, which can result in further treatments and procedures, as 
well as prolongation of healing. There is a need to develop improved techniques in acute burn 
management1 
Adipose Derived Regenerative Cells (ADRCs) are of emerging interest in the application of wound 
healing. Cells obtained from adipose tissue have been shown to inhibit inflammation2-5 , promote 
angiogenesis5-7, 7-13, stimulate recruitment of endogenous regenerative cells14, 15 and promote salvage of 
damaged cells2, 5, 16. On the basis of these properties, several preclinical studies have been performed 
using freshly isolated and cultured adipose-derived cells in a number of animal models of normal and 
impaired wound healing. The data consistently show improvement of epithelialization and wound healing. 
ADRCs are an advantageous resource because they can be found in abundant quantities, they can be 
harvested with a minimally invasive procedure17, 18, and they can be safely and effectively transplanted 
into an autologous host. 
The Celution® System is designed to process lipoaspirated tissue to separate ADRCs from adipose tissue 
by enzymatic disassociation of the tissue and using buoyancy differences and centrifugation to separate 
and then concentrate the ADRCs from lipid containing adipocytes. When ADRCs are prepared using the 
Celution® System, the resultant cell suspension contains all of the components naturally occurring in the 
native tissue. Preparation of autologous ADRCs for delivery using the Celution® System involves no cell 
culture. The prepared ADRC dose can be administered to the same patient within four hours.  
This study is a prospective, open-label, parallel group, usual care controlled, multi-center randomized 
(2:1, active: usual care alone) safety and feasibility study targeting thermal burns. Subjects will have at 
least one deep partial or full thickness burn wounds of > 250 cm2 that is to be autografted with a split 
thickness skin graft (STSG). Subjects randomized to ADRCs will undergo small volume fat harvest (100 
to 150 mL) performed at initiation of general anesthesia for scheduled burn surgery followed by 
intravenous delivery of ADRCs within 4 hours following completion of Celution processing. The 
lipoaspirate will be processed in the Celution® System to isolate and concentrate ADRCs. 
Following informed consent and initial screening assessments, eligible subjects will undergo pre-
operative testing. On the procedure day, subjects will be randomized to ADRCs (with usual care) or usual 
care alone. Low volume lipoharvest will only be performed on subjects randomized to ADRCs in order to 
obtain 100-150 mL lipoaspirate, which will then be transferred to the Celution® System for processing to 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 32 of 48 
Date: 
May 14, 2018 
isolate and concentrate ADRCs for same-day administration. All treatment will be delivered in a total 
volume of 10 mL which will be delivered by slow intravenous administration. 
Following surgery, subjects will be evaluated at several intervals up to 52 weeks to assess safety and 
efficacy as measured by direct measurement of wound healing.  
9.2 
Assessment of risks of the proposed Investigation 
The areas of risk include those of adipose tissue harvest and ADRCs delivery.  
9.3 
Risks 
The primary risks associated with adipose tissue harvest are bleeding and infection associated with the 
removal of the adipose tissue (fat harvesting procedure) along with the potential risk of infection 
associated with intravenous delivery of ADRCs.  
Tissue harvest by syringe-based manual aspiration has been used as a source for ADRCs in the 344 
subjects in 7 clinical trials with the Celution system. Adverse events were those commonly associated 
with liposuction such as discomfort and ecchymosis. The only related serious adverse event reported was 
a single event of rectus sheath hematoma which was associated with the use of a glycoprotein IIb/IIIa 
inhibitor. The patient had unremarkable recovery. Fat harvest has been demonstrated to be feasible and is 
associated with an acceptable safety profile. The volume of adipose tissue removed in these studies 
generally varied between 150 mL and 450 mL. In the proposed feasibility and safety trial in burn patients 
a target volume between 100 to 150 mL of adipose tissue is to be removed and processed for ADRCs. 
9.4 
Intravenous Delivery Risk Analysis and Management 
Risks involved with intravenous delivery of ADRCs cells include: 
 Embolism 
 Infection 
The preclinical studies described herewith demonstrate no evidence of serious adverse events associated 
with ADRCs delivered intravenously, topically, subcutaneously, or intraarticularly. The clinical trial 
studies also have not reported significant safety issues when ADRCs are delivered subcutaneously, 
intraarticularly or intra-arterially. As in other trials applying intravascular administration of ADRCs, the 
ADRC product will be passed through a 47µm filter as part of the infusion process in order to further 
minimize risk of embolism. However, the possibility of infection exists with any percutaneous procedure. 
However, current experience in multiple clinical studies has not revealed any patient infections 
association with ADRCs delivery.  
To mitigate potential risk of infection a gram stain of the ADRCs doses will be performed and must be 
negative in order to proceed with intravenous administration. A sample will be sent to the hospital 
laboratory for BacT (or equivalent) culture including aerobic microorganisms and sensitivity. All 
procedures related the Celution® System and cell counting are performed in aseptic conditions. If a culture 
result is positive for microbial activity, the investigator will be immediately notified. The study patient 
will be evaluated and standard clinical treatments of infection for patients with burn wound injury should 
be followed including antibiotics as deemed appropriate by the study investigator.  
9.5 
Celution® System and Delivery Device Risk Analysis and Management 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 33 of 48 
Date: 
May 14, 2018 
The investigators and all study personnel will be trained in the details of all aspects of the study 
procedures relevant to their particular area of responsibility.  
 Train investigators and all study personnel in the details of the operation of the Celution System 
and Cytori Work Instructions for ancillary procedures and devices such as cell counting and 
intravenous delivery. 
 Inspect the package integrity and sterility indicators on all disposables used with the devices and 
maintain sterility of the fluid paths. 
 Follow Instructions for Use for the Celution® System, including all warnings, precautions and 
contraindications. 
9.6 
Fat Harvest Risk Analysis 
The risks of standard small volume liposuction in healthy patients are known and are minimal and 
recovery is usually fast. Following standard liposuction the following effects can be expected: 
Common 
 Edema and redness of the liposuction areas for a few days 
 Moderate contusion of the liposuction areas for a few months 
 
Uncommon 
 Persistent edema 
 Persistent bleeding 
 Hematoma  
 Visible puncture sites 
 
Rare 
 Infection 
 Deep Vein thrombosis (DVT) 
 Persistent bleeding requiring transfusion 
9.6.1 Fat Harvest Risk Management 
The Investigators and all study personnel will be trained in the details of all aspects of the study 
procedures. Standardization of fat harvest techniques is critical to a good clinical outcome. To minimize 
risks and increase the chances of a favorable clinical outcome the following measures are required for the 
liposuction procedure: 
 Performed by an appropriately licensed and credentialed physician  
 Monitoring of vital signs throughout the procedure 
 Sterile technique is followed throughout 
 The adipose tissue is handled gently at all times 
 HGB, HCT prior to and 1-2 hours post-procedure  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 34 of 48 
Date: 
May 14, 2018 
 To sufficiently induce local vasoconstriction/hemostasis during the fat harvest procedure, a 
minimum of 500 mL and a recommended maximum of 2000 mL of tumescent fluid is used 
containing:  
o 500 mL of Lactated Ringers solution 
o 20-50 mL of 1% Lidocaine 
o 1 mg of epinephrine  
 A blunt 14 to 16 gauge LAMIS infiltrator (or equivalent) will be used for infiltration with 
tumescent solution  
 After approximately 10 minutes, the adipose tissue may be harvested through the same incision, 
using the aspiration cannula attached to a syringe 
 A blunt cannula with a minimum inner diameter of 3 mm is preferred for lipoaspiration. 
 Lipoaspiration is done manually using a syringe (60 mL Toomey syringe is preferred); no machine 
aspiration is permitted. 
 Monitoring for prevention or early detection of bleeding:  
 Enrollment of only patients who qualify per the inclusion / exclusion criteria defined in the 
protocol) including screening blood work 
 Strict adherence to the study protocol 
 Standard of care for the monitoring and treatment of subjects who experience any adverse event 
for liposuction 
 Target volume of adipose tissue is limited to approximately 100-150 mL  
 Close surgical incision with appropriate suture 
 Apply pressure bandage immediately upon conclusion of tissue harvest 
Fat harvest should NOT be performed on patients who have received any anticoagulant within 1 hour of 
the procedure, substantial anticoagulation (eg: GIIb/IIIa inhibitor class drugs) within two weeks prior to 
fat harvest, or who have an abnormal PTT. 
 
9.7 
Overall Study Risk Management 
The following measures implemented by Cytori will minimize the risks associated with patients’ 
participation in clinical studies: 
 All examinations, treatment procedures, and interpretation of clinical data generated during the 
study is directed, overseen and analyzed by an appropriately licensed and credentialed physician 
who has been trained to the clinical study protocol. 
 Protocol and training programs to ensure that the study personnel at Cytori and at the clinical sites 
have a strong knowledge and understanding of the clinical protocol, including patient selection 
criteria and procedure requirements. 
 Investigators are trained to the procedure requirements in the protocol, and the Instructions for Use 
for the Celution® System. 
 Clearly defined inclusion and exclusion criteria to ensure that only properly selected patients will 
be enrolled in the clinical study. 
 The protocol is designed so that patient treatment and follow-up procedures will be consistent with 
those of the clinically established standard of care. 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 35 of 48 
Date: 
May 14, 2018 
 
9.8 
Assessment of the Benefits of the Proposed Investigation 
This clinical investigation is designed as a safety and feasibility study. Therefore, it is not known at this 
time whether any direct subject benefit can be expected.  
Patients with significant thermal burn injury typically require, on average, approximately 1 to 1.5 days of 
in-hospital care for each 1% of burned TBSA. Burn treatment involves labor-intensive procedures over a 
long period of time. For the patient, this includes substantial pain and morbidity from repeated excisions 
and harvest of skin autografts. Currently available preclinical data indicate that ADRC treatment may 
improve the quality of granulation tissue formed following escharectomy, promote more rapid re-
epithelialization of the burn wound and reduce hypertrophic scar formation. These effects have the 
potential to improve the efficiency of integration of an autologous STSG into the wound site (commonly 
referred to as ‘graft take’). They also have the potential to accelerate the rate at which the meshed 
component of the skin graft fills in with new epithelium. Earlier wound closure and improved graft take 
will likely lead to reduced risk of infection, shorter duration of stay, reduced rate of hypertrophic scarring 
formation and contracture, and reduced need for repeat procedures such as re-grafting and subsequent 
procedures to address hypertrophic scarring. 
9.9 
Consideration of Patient Preference information 
None can be provided at this time. 
9.10 Assessment of Uncertainty 
The key source of the uncertainty in the available evidence is the safety of the procedure in burn wound 
subjects and the level of potential effect on wound healing and the improvement in the clinical course of 
the subject. The safety profile of liposuction in subjects with burn wounds has not been established. 
Liposuction, in order to obtain ADRCs via the Celution system, has been used in seriously ill subjects in 
several studies that evaluated the effects of ADRCs on congestive heart failure and in subjects with an 
acute myocardial infarction (MI) within a 72 hour window post MI. No adverse events occurred 
secondary to liposuction other than the one subject with a rectus sheath hematoma whose had received a 
glycoprotein IIb/IIIa inhibitor. The procedure of low volume liposuction appears to be tolerated in 
subjects with significant myocardial decomposition. The safety of the subjects in this trial will be 
evaluated within a staggered enrollment with safety evaluations as well as by a Data Monitoring 
Committee (DMC). 
The extent of benefit to subjects is unknown as no other clinical trial using intravenously administered 
ADRCs in the treatment of burn wounds has been done. Preclinical data generated in animal models of 
burn wounds suggests that wound healing should be accelerated. 
9.11 Conclusions 
 
The overall risk benefit profile with the proposed safety assessment measures makes the balance of risk to 
benefit sufficient to proceed with this clinical trial. 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 36 of 48 
Date: 
May 14, 2018 
10 
STATISTICAL METHODS AND DATA ANALYSIS 
The RELIEF Trial is a multi-center, open-label, randomized, usual care controlled study to evaluate the 
feasibility and safety of ADRCs with usual care compared to usual care alone in subjects with thermal 
burns. The primary endpoint will be safety and feasibility. 
The ITT population will be used for the primary analysis; the analysis will also be presented in the PTE 
population.  
10.1 General Considerations 
All statistical tests will be two-sided and statistical significance will be assessed with respect to a nominal 
p-value <0.05. Prior to the data base lock, a separate statistical analysis plan (SAP) will be finalized. Any 
deviations from the planned analyses will be documented and justified in the final clinical/statistical study 
report. The SAP will detail all planned analyses and will serve as a statistical programming requirements 
document.  
10.2 Determination of Sample Size 
The objective of the pilot study is to evaluate the safety and feasibility of autologous Adipose-Derived 
Regenerative Cells (ADRCs) for the treatment of thermal wounds. The sample size of up to 15 subjects 
(each subject contributing up to 3 wounds to the dataset) is not powered to test specific hypotheses. The 
sample size is proposed to provide preliminary safety and feasibility data in order to design a larger study 
with sufficient power to test a hypothesis regarding benefits of ADRCs.  
10.3 Data Analyses 
Safety and efficacy endpoints will be summarized by treatment group using descriptive statistics (n, mean, 
SD, median, minimum and maximum), for quantitative variables and frequencies and percentages for 
categorical variables. 
For quantitative efficacy variables, the change from baseline to each post-baseline time point will be 
analyzed using Student’s t-test. For each endpoint, the treatment groups will be compared using two-sided 
tests at the alpha=0.05 level of significance. 
The final dataset includes grafts with different mesh size (for example; 2:1 and 3:1). While the study is 
not powered for analysis of efficacy, data analysis for comparison between subjects receiving usual care 
and those receiving usual care plus ADRCs with respect to exploratory endpoints associated with healing 
(e.g.: percent epithelialization, pigmentation, hardness, Vancouver Scar Scale) will be stratified by mesh 
size (for example: 2:1, 3:1, 4:1, and all grouped). 
Subjects randomized to the ADRC-treatment arm who undergo liposuction but who are not treated with 
ADRCs because the ADRCs do not meet release criteria may be followed up for the full duration of the 
study. Such subjects will be (a) included in the full data analysis for feasibility, (b) analyzed separately for 
safety, (c) analyzed in the ITT group for efficacy, and (d) excluded from the PTE group for efficacy. 
10.3.1 Primary Endpoint Analysis 
The primary endpoints for the study are safety and feasibility. 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 37 of 48 
Date: 
May 14, 2018 
Safety endpoint will be summarized by treatment group using quantitative and descriptive statistics of 
adverse events. Adverse events will be assessed according to the NIH Common Terminology Criteria for 
Adverse Events (CTCAE) v4.0 for scale grading adverse events. Related adverse events will be analyzed 
separately for those related to ADRCs and to the delivery of ADRCs (i.e. intravenous delivery), and for 
those related to tissue harvest. 
Feasibility will address the following: 
 Ability to perform tissue harvest and obtain 100-150 mL of adipose tissue  
 Completion of dose preparation with the target dose 
 Ability to deliver ADRCs via intravenous administration 
 Successful secondary endpoint evaluations 
10.3.2 Key Secondary and Exploratory Endpoint Analysis 
The key secondary endpoints are  
 Percent epithelialization 
 Graft take 
 Proportion of population with complete wound closer 
Epithelialization will be assessed by surgeon visual evaluation and blinded independent review of 
standardized digital photographs. Graft take will be assessed as the area over which vascularization is 
evident, and sufficient anchorage to the underlying tissue exists to support epidermal growth. Take will be 
expressed as a percentage of the area originally covered by the graft. Percent take is estimated separately 
for each of the grafted study sites. The proportion of subjects with complete wound healing will be 
determined and is defined as skin re-epithelialization without drainage or dressing requirements. 
All other secondary endpoints will be treated as exploratory. P-values for each analysis will be computed 
separately, without any corrections for multiple comparisons. These analyses will be considered as part of 
the totality of the evidence concerning the safety and effectiveness of the product.  
10.4 Background, Demographic and Concomitant Medication Analyses 
Demographic data, medical history, concomitant disease and concomitant medication will be summarized 
by means of descriptive statistics (n, mean, SD, median, minimum and maximum) or frequency tables. 
10.5 Withdrawal, ITT, PTE 
Reasons for withdrawal pre- and post-randomization will be summarized. The treatment analyses will be 
performed on intent-to-treat basis as well as on a per-treatment-evaluable basis, as defined below: 
Intent-to-Treat (ITT): All randomized subjects; randomization will occur on procedure day prior to the 
tissue harvest procedure. Subjects will be included in the analysis according to the treatment assigned if 
population is different than PTE. 
Per-Treatment-Evaluable (PTE): All enrolled subjects who have day 5 follow-up information available. 
10.6 Handling of Missing Data 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 38 of 48 
Date: 
May 14, 2018 
Given the relatively small sample, missing data will not be imputed. 
10.7 Protocol Deviations 
Deviations from the protocol, including violations of inclusion/exclusion criteria, will be assessed as 
“minor” or “major” by the Sponsor. Deviations will be defined prior to un-blinding. 
10.8 Data Monitoring Committee 
The independent Data Monitoring Committee (DMC) will be comprised of burn specialists and a 
biostatistician who are not participants in the study. The DMC will be provided with all safety data as 
well as efficacy data for the primary endpoint in order to fully evaluate the benefit to risk profile of the 
study procedures. The DMC will be responsible for the review of the data and generation of 
recommendations on the conduct of the trial. 
The DMC will be asked to review data and generate recommendations after 5, 10, and 15 subjects have at 
least 1 week of follow-up. Enrollment after the first 5 subjects enrolled in active treatment may continue 
only after the DMC has completed its safety review and recommends continuation.  
11 
ADVERSE EVENTS / SERIOUS ADVERSE EVENTS 
11.1 Definitions 
An Adverse Event (AE) is defined as any undesirable experience occurring to a Subject during the 
course of the study, whether or not it is related to the test material or the study procedure. Expected 
adverse events are those that are listed as known risks of the tissue harvest or ADRC application 
procedure including those described in this protocol or the informed consent. 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that: 
 Results in death 
 Is life-threatening 
 Requires or prolongs Subject hospitalization 
 Results in persistent or significant disability or incapacity 
 Is an important medical event(s) that may not be immediately life-threatening or result in death or 
hospitalization but that may jeopardize the Subject or require intervention to prevent one of the 
above outcomes 
 Is a congenital anomaly/birth defect. 
Medical and scientific judgment should be exercised in deciding whether a case is serious and whether 
expedited reporting is appropriate. 
Pain and ecchymosis/hemorrhage around the fat harvest site are expected and should not be recorded as 
an adverse event unless meeting one or more of the following criteria:  (a) serious adverse event (SAE), 
(b) greater severity than expected according to Investigator clinical judgment, or (c) hemorrhage requiring 
evacuation. 
An Unanticipated Adverse Device Effect (UADE) is defined as any serious adverse effect on the health 
and safety or any life-threatening problem or death caused by, or associated with the Celution® system 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 39 of 48 
Date: 
May 14, 2018 
device, if that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application or any other unanticipated serious problem with the 
Celution® system device that relates to the rights, safety or welfare of subjects.   
11.2 Procedures for AE Reporting 
Adverse events will be assessed according to the NIH Common Terminology Criteria for Adverse Events 
(CTCAE) v4.0 for scale grading adverse events. 
All AEs (including SAEs and UADEs) will be recorded by the investigator or designee on the appropriate 
electronic case report form (eCRF). Events that occur prior to the tissue harvest, including those that are 
considered serious, are to be recorded in the medical history. Events, including SAEs, which occur after 
tissue harvest procedure day, are to be recorded on the AE eCRF. The investigator will evaluate the 
relationship of the adverse event to both the test material and study procedure as unrelated, unlikely, 
possibly, probably, or definitely related and will record the findings, including all pertinent details of the 
event on the eCRF.  
The investigator shall submit to the sponsor and to the reviewing IRB a report of any UADE occurring 
during an investigation as soon as possible, but in no event later than 10 working days after the 
investigator first learns of the effect. 
In addition, the Investigator or designee will report any serious adverse events occurring during this study 
to the Cytori Medical Monitor as soon as possible, but no later than 24 hours after the Investigator first 
identifies the adverse event. 
The Investigator will take appropriate measures to ensure the subject’s well-being and document these 
measures on the appropriate eCRF.  
All serious adverse events experienced will be monitored until the event has resolved, any abnormal 
laboratory values have returned to baseline or stabilized at a level acceptable to the Investigator and 
Medical Monitor, or until there is a satisfactory explanation for the changes observed. 
 
12 
EMERGENCY DEVIATION FROM THE PROTOCOL 
In case of an emergency threatening the continued well being of the Subject, the Investigator may deviate 
from the protocol. The circumstances necessitating the deviation and the intervention(s) required will be 
recorded on the subject’s source documentation. The Sponsor must be notified as soon as possible, but no 
later than 5 days after event(s) occurred. The site’s Institutional Review Board (IRB) should be notified as 
per the IRB regulations. 
13 
REGULATORY OBLIGATIONS AND STUDY REQUIREMENTS 
13.1 FDA and Institutional Review Board Approval 
Study initiation will not take place until the following regulatory requirements are met: 
 
Food and Drug Administration (FDA) approval with accompanying approval letter.  
 
Local Institutional Review Board (IRB) full approval with accompanying approval letter. 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 40 of 48 
Date: 
May 14, 2018 
 
13.2 Informed Consent 
Written informed consent will be obtained from all subjects, or their legally authorized representative, 
prior to the initiation of any study specific procedures. No tests or procedures required in this protocol 
that are outside the standard practice for treating thermal wounds will be initiated prior to obtaining 
written informed consent. The original IRB approved informed consent form will be filed in the 
Investigator Site Files according to site procedure. 
13.3 Monitoring Procedures and Data Management 
13.3.1 Site Qualification 
A site qualification visit will be performed to evaluate site facilities, Investigator qualifications, adequacy 
of staffing, and understanding of clinical and regulatory requirements. 
13.3.2 Site Training 
All Investigators and appropriate study staff will be required to participate in a site training (or initiation if 
appropriate) to provide orientation and training to the Celution System, the RELIEF Protocol, eCRFs and 
other study related documents and procedures.  
13.3.3 Monitoring 
During the course of the study, a representative of the Sponsor will make site visits to review protocol 
compliance, compare eCRFs and individual Subject’s medical records, assess test article accountability, 
and ensure that the study is being conducted according to pertinent regulatory requirements. eCRF entries 
will be verified with source documentation. The review of medical records will be performed in a manner 
to ensure that Subject confidentiality is maintained. 
 
Regulatory authorities (United States Food and Drug Administration) and/or the Sponsor’s Clinical 
Quality Assurance Group may wish to carry out source data checks and/or on-site audit inspections. 
Direct access to source data will be required for these inspections and audits; they will be carried out 
giving due consideration to data protection and medical confidentiality.  
13.3.4 Reporting Requirements 
The following reports are required of the Investigator: 
 eCRFs for each Subject entered into the study (including all screen failures) 
 Reports of any SAEs  or UADEs within 24 hours of becoming aware of events 
 Final report at the conclusion of the study 
 Progress reports to the Sponsor and IRB at regular intervals, annually at a minimum  
 Report to the Sponsor, within 5 working days, of approval withdrawal by the reviewing IRB 
 Report to the Sponsor and IRB of any emergency changes made to the protocol to protect the life 
or physical well being of a Subject no later than 5 working days after the emergency occurred 
13.3.5 Data Management 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 41 of 48 
Date: 
May 14, 2018 
Data management will be conducted by the Sponsor or designee, and will include a data management plan 
and data verification guide developed according to protocol requirements. 
13.4 Study Center and Investigator Requirements 
To protect the rights and welfare of Subjects, the study will be conducted in conformance with the 
Declaration of Helsinki, the guidelines on GCPs, Code of Federal Regulations (21 CFR 11, 50, 56, 812, 
814 and 820) and applicable local laws and regulations pertaining to the conduct of the study and the 
protection to human Subjects. 
All Investigators, sub-investigators and study personnel are required to read and follow the protocol, as 
well as any literature that accompanies the products, prior to conducting the study procedure for the first 
time. In addition, all Investigators will sign and date the Investigator Statement Page of this protocol. All 
Investigators participating in this study will be trained in the proper use of the study procedure and in the 
components of the RELIEF protocol. 
The Principal Investigator is ultimately responsible for the conduct of this study; however, he/she may 
designate a member of his/her staff to assist with the collection of data and completion of eCRFs. The 
designee(s) will be documented on an authorization form that is signed by the PI and kept in the 
Regulatory Binder, to be updated as necessary. Current copies of the authorization form will be forwarded 
to the Sponsor. 
Obtaining informed consent in accordance with national policy is mandatory for Subject participation. All 
Subject data is kept confidential and procedures will be implemented to ensure that Subject confidentiality 
is not compromised. 
If additional materials are used for screening and recruitment or provided to study Subjects (i.e. 
advertisements, recruitment materials) they must be approved by Cytori Therapeutics and the Institutional 
Review Board at the clinical site prior to use. Documentation of the approved informed consent must be 
provided to Cytori prior to study commencement at the clinical site. 
After a Subject (or legal next of kin) has signed the Informed Consent Form, an eCRF will be initiated. 
After this point, the reason(s) must be documented on the report form for any Subject who has dropped, 
withdraws, or for any reason cannot complete this study. 
13.4.1 Study Center Requirements 
Due to the nature of the RELIEF Protocol, centers will be considered for participation only if they meet 
the following minimum facility requirements: 
 Familiarity with FDA authorized IDE and/or IND Clinical Trials within the United States 
 Pharmacy or laboratory (or qualified designee) capable of performing clinical trial randomization 
and cell dose preparation 
 Ability to adhere to strict compliance with the clinical protocol for all study related procedure and 
observations  

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 42 of 48 
Date: 
May 14, 2018 
14 
PUBLICATIONS 
Following completion of the study, Cytori will present the study data in a clinical study report that will be 
delivered to the FDA according to US regulations. 
When investigators external to Cytori conduct analyses of Company-sponsored study data or develop 
other works that use our data, we maintain the right to be informed of any plans for publication and to 
review any resulting works, including abstracts, presentations, or manuscripts, before they are submitted. 
We will return our comments to the authors in a timely manner so that they may submit the work for 
publication. In the event the investigator wishes to present or publish any study data (partial or complete), 
Cytori requests that he/she must submit the presentation / publication draft to Cytori for review prior to 30 
days of the planned submission or presentation.  
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 43 of 48 
Date: 
14 May 2018 
 
15 
APPENDIX A:  SCHEDULE OF PROCEDURES 
 
Day -2 
to Day -
1 
Procedure 
Day 1 
At First 
Dressing 
Change 
Day 10 
(±2d)1 
Week 2 
(±3d) 
Week 3 
(±3d) 
Week 4 
(±3d) 
Week 8 
(±7d) 
Week 12 
(±7d) 
Week 26 
(±14d) 
Week 52 
(±21d) 
Informed consent 
X 
 
 
 
 
Medical history (including 
demographics) 
X 
 
 
 
 
 
 
 
 
 
 
Physical examination (including 
height and weight at screening) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, HR, Temp, RR) 
X 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Testing5 
X 
X 
X 
 
 
 
 
Pregnancy test (urine) 
X 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Digital photography of wounds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Low Volume Lipoharvest 
X 
 
 
 
 
Microbiology3 
X 
 
 
 
 
ADRC dose prep and delivery 
X 
 
 
 
 
% Epithelialization   
X 
X 
X 
X 
X 
 
 
 
Biomarkers4 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
% Graft Take 
X 
X 
X 
X 
X 
 
 
 
Transepithelial water loss 
 
X 
X 
X 
 
 
 
Wound Pain VAS 
X 
X 
X 
X 
X 
 
 
 
Pruritis VAS 
 
X 
X 
X 
X 
X 
X 
POSAS questionnaires 
 
X 
X 
X 
X 
X 
X 
Vancouver Scar Scale 
 
X 
X 
X 
Skin elasticity measurement 
 
X 
X 
X 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 44 of 48 
Date: 
14 May 2018 
 
 
Day -2 
to Day -
1 
Procedure 
Day 1 
At First 
Dressing 
Change 
Day 10 
(±2d)1 
Week 2 
(±3d) 
Week 3 
(±3d) 
Week 4 
(±3d) 
Week 8 
(±7d) 
Week 12 
(±7d) 
Week 26 
(±14d) 
Week 52 
(±21d) 
Skin pigmentation 
 
X 
X 
X 
Skin hardness 
 
X 
X 
X 
Complete Wound Closure 
 
X 
X 
X 
X 
X 
 
 
Randomization 
X 
 
 
 
 
1Day 10 assessments performed only if wound dressing is being changed between days 8 and 12. 2 Vital signs will be monitored according to institutional procedures. 3Microbiological testing of dose 
samples (ADRCs) at baseline (prior to ADRCs administration). 4Biomarkers will be measured in serum from 4 to 5 ml of whole blood that is collected, centrifuged, separated into 500-µL aliquots, and 
stored at -80°C  will be collected at baseline (prior to ADRC administration), days 5 and 10 and weeks 2, 3, 4, 8 and 12 post ADRC administration. 5 Laboratory testing will include CBC with Platelets, 
INR, PTT,Electrolytes, alkaline phosphatise, AST, ALT, bilirubin, total protein, albumin, BUN and creatinine and, for patients with diabetes only, evaluation of HbA1c levels (see Exclusion Criterion 
10).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 45 of 48 
Date: 
14 May 2018 
 
 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 46 of 48 
Date: 
14 May 2018 
 
 
16 
REFERENCES 
 
 
(1)  Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, Chan RK, Christy RJ, 
Chung KK. Burn wound healing and treatment: review and advancements. Crit Care 
2015;19:243. 
 
(2)  Feng Z, Ting J, Alfonso Z, Strem BM, Fraser JK, Rutenberg J, Kuo HC, Pinkernell K. Fresh 
and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate 
ischemia-reperfusion-induced acute kidney injury. Nephrol Dial Transplant 2010;25:3874-84. 
 
(3)  Premaratne GU, Ma LP, Fujita M, Lin X, Bollano E, Fu M. Stromal vascular fraction 
transplantation as an alternative therapy for ischemic heart failure: anti-inflammatory role. J 
Cardiothorac Surg 2011;6:43. 
 
(4)  Foubert P, Gonzalez AD, Teodosescu S, Berard F, Doyle-Eisele M, Yekkala K, Tenenhaus M, 
Fraser JK. Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A 
Comparison of Two Delivery Methods. Adv Wound Care (New Rochelle ) 2016;5:288-98. 
 
(5)  Nambu M, Kishimoto S, Nakamura S, Mizuno H, Yanagibayashi S, Yamamoto N, Azuma R, 
Nakamura S, Kiyosawa T, Ishihara M, Kanatani Y. Accelerated wound healing in healing-
impaired db/db mice by autologous adipose tissue-derived stromal cells combined with 
atelocollagen matrix. Ann Plast Surg 2009;62:317-21. 
 
(6)  Fu X, Fang L, Li H, Li X, Cheng B, Sheng Z. Adipose tissue extract enhances skin wound 
healing. Wound Repair Regen 2007;15:540-8. 
 
(7)  Altman AM, Yan Y, Matthias N, Bai X, Rios C, Mathur AB, Song YH, Alt EU. IFATS 
collection: Human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold 
enhance wound repair in a murine soft tissue injury model. Stem Cells 2009;27:250-8. 
 
(8)  Hao C, Shintani S, Shimizu Y, Kondo K, Ishii M, Wu H, Murohara T. Therapeutic 
angiogenesis by autologous adipose-derived regenerative cells: comparison with bone marrow 
mononuclear cells. Am J Physiol Heart Circ Physiol 2014;307:H869-H879. 
 
(9)  Kondo K, Shintani S, Shibata R, Murakami H, Murakami R, Imaizumi M, Kitagawa Y, 
Murohara T. Implantation of adipose-derived regenerative cells enhances ischemia-induced 
angiogenesis. Arterioscler Thromb Vasc Biol 2009;29:61-6. 
 (10)  Murohara T, Shintani S, Kondo K. Autologous adipose-derived regenerative cells for 
therapeutic angiogenesis. Curr Pharm Des 2009;15:2784-90. 
 (11)  Foubert P, Barillas S, Gonzalez AD, Alfonso Z, Zhao S, Hakim I, Meschter C, Tenenhaus M, 
Fraser JK. Uncultured adipose-derived regenerative cells (ADRCs) seeded in collagen scaffold 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 47 of 48 
Date: 
14 May 2018 
 
improves dermal regeneration, enhancing early vascularization and structural organization 
following thermal burns. Burns 2015;41:1504-16. 
 (12)  Foubert P, Doyle-Eisele M, Gonzalez A, Berard F, Weber W, Zafra D, Alfonso Z, Zhao S, 
Tenenhaus M, Fraser JK. Development of a Combined Radiation and Full Thickness Burn 
Injury Minipig Model to Study the Effects of Uncultured Adipose-Derived Regenerative Cell 
Therapy in Wound Healing. Int J Radiat Biol 2016;1-35. 
 (13)  Blanton MW, Hadad I, Johnstone BH, Mund JA, Rogers PI, Eppley BL, March KL. Adipose 
stromal cells and platelet-rich plasma therapies synergistically increase revascularization during 
wound healing. Plast Reconstr Surg 2009;123:56S-64S. 
 (14)  Kuo YR, Wang CT, Cheng JT, Kao GS, Chiang YC, Wang CJ. Adipose-Derived Stem Cells 
Accelerate Diabetic Wound Healing Through the Induction of Autocrine and Paracrine Effects. 
Cell Transplant 2016;25:71-81. 
 (15)  Kosaraju R, Rennert RC, Maan ZN, Duscher D, Barrera J, Whittam AJ, Januszyk M, Rajadas J, 
Rodrigues M, Gurtner GC. Adipose-Derived Stem Cell-Seeded Hydrogels Increase 
Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds. Tissue Eng Part 
A 2016;22:295-305. 
 (16)  Ebrahimian TG, Pouzoulet F, Squiban C, Buard V, Andre M, Cousin B, Gourmelon P, 
Benderitter M, Casteilla L, Tamarat R. Cell therapy based on adipose tissue-derived stromal 
cells promotes physiological and pathological wound healing. Arterioscler Thromb Vasc Biol 
2009;29:503-10. 
 (17)  Fraser JK, Hicok KC, Shanahan R, Zhu M, Miller S, Arm DM. The Celution System: 
Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed 
System. Adv Wound Care (New Rochelle ) 2014;3:38-45. 
 (18)  Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem 
cells for biotechnology. Trends Biotechnol 2006;24:150-4. 
 (19)  Huang SP, Huang CH, Shyu JF, Lee HS, Chen SG, Chan JY, Huang SM. Promotion of wound 
healing using adipose-derived stem cells in radiation ulcer of a rat model. J Biomed Sci 
2013;20:51. 
 (20)  Nambu M, Ishihara M, Nakamura S, Mizuno H, Yanagibayashi S, Kanatani Y, Hattori H, 
Takase B, Ishizuka T, Kishimoto S, Amano Y, Yamamoto N, Azuma R, Kiyosawa T. 
Enhanced healing of mitomycin C-treated wounds in rats using inbred adipose tissue-derived 
stromal cells within an atelocollagen matrix. Wound Repair Regen 2007;15:505-10. 
 (21)  Henry TD, Pepine CJ, Lambert CR, Traverse JH, Schatz R, Costa M, Povsic TJ, David AR, 
Willerson JT, Kesten S, Perin EC. The Athena trials: Autologous adipose-derived regenerative 
cells for refractory chronic myocardial ischemia with left ventricular dysfunction. Catheter 
Cardiovasc Interv 2016. 

Cytori Therapeutics, Inc.  
Doc #: CLP0010_04 RELIEF Protocol 
Page 48 of 48 
Date: 
14 May 2018 
 
 (22)  Ruiz-Castilla M, Roca O, Masclans JR, Barret JP. RECENT ADVANCES IN BIOMARKERS 
IN SEVERE BURNS. Shock 2016;45:117-25. 
 (23)  Ulrich D, Noah EM, Burchardt ER, Atkins D, Pallua N. Serum concentration of amino-terminal 
propeptide of type III procollagen (PIIINP) as a prognostic marker for skin fibrosis after scar 
correction in burned patients. Burns 2002;28:766-71. 
 (24)  Ulrich D, Noah EM, von HD, Pallua N. TIMP-1, MMP-2, MMP-9, and PIIINP as serum 
markers for skin fibrosis in patients following severe burn trauma. Plast Reconstr Surg 
2003;111:1423-31. 
 (25)  Akita S, Yoshimoto H, Ohtsuru A, Hirano A, Yamashita S. Autologous adipose-derived 
regenerative cells are effective for chronic intractable radiation injuries. Radiat Prot Dosimetry 
2012;151:656-60. 
 (26)  Atalay S, Coruh A, Deniz K. Stromal vascular fraction improves deep partial thickness burn 
wound healing. Burns 2014;40:1375-83. 
 (27)  Marino G, Moraci M, Armenia E, Orabona C, Sergio R, De SG, Capuozzo V, Barbarisi M, 
Rosso F, Giordano G, Iovino F, Barbarisi A. Therapy with autologous adipose-derived 
regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial 
disease. J Surg Res 2013;185:36-44. 
 (28)  Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, 
Yoshimura K, Gimble JM. Stromal cells from the adipose tissue-derived stromal vascular 
fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the 
International Federation for Adipose Therapeutics and Science (IFATS) and the International 
Society for Cellular Therapy (ISCT). Cytotherapy 2013;15:641-8.