Clinical trial NCT02779205: Child's Adipose Cells: Capacity of Tissue Regeneration
Official title: Evaluation of Tissue Regeneration Potential (in the Skin) of Child's Adipose Cells During the Development.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Burns
Keywords: Cell therapy
Stromal Cells
Stem cells
Adipose tissue
Children
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2016-05-20
Enrollment: 38
Sex: ALL
Minimum age (years): 37
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The beneficial effect related to the administration of adipose tissue-derived stromal cells (ADSC) is demonstrated in various situations of physiological and pathological wound healing, thus opening a new field for cell therapy. Despite the use of new technologies, management of burns in children as well as congenital malformation such as hypospadias and cleft lip and/ or cleft palate can lead to aesthetic and functional sequelae requiring multiple surgical procedures. Cell therapy based on the administration of the ADSC seems a promising issue in such indications, however, to date no study has been conducted with ADSC from a pediatric population. An initial study (Protocol 0808203) allowed investigors to obtain the first samples of adipose tissue from children and to conduct an in vitro comparative study on the characterization and properties of the ADSC from children compared to adults. In the continuity, this second study aims to complete knowledge on the efficacy and safety of children ADSC cell therapy assessed in an animal model of skin wound healing developed in the lab.

Detailed description: Through this study, the medium term objective is to approach a clinical protocol for treatment of pathological scars in developing an appropriate way to deliver ADSC for a future clinical application, while ensuring the safety of such procedure.

The primary goal of this work is to determine whether ADSC from children prepared according to Good Manufacturing Practice (GMP), is associated with an improvement of wound healing in vivo as demonstrated with adult ADSC. To answer this question, 40 samples of adipose tissue of children obtained from settled surgery (inguinal hernia and vesico-ureteral reflux by suprapubic way) will be performed within the 2 groups of children; 0 to 1 year and 2 to 13 years, defined from data acquired in the previous protocol. Wound healing will be evaluated in a nude mouse model of skin burn. A macroscopic analysis will be carried out with two indexes described in the literature (re-epithelialization and scar contraction) and expressed as a percentage of the initial lesion at different times (3 days, 7 days, 10 days, 14 days, 21 days, 30 days). A microscopic analysis will be conducted to determine the rate of re-epithelialization (day 7) and the evolution of the skin structural parameters (dermal and epidermal thickness, density of collagen, inflammatory infiltration). These indexes will be defined in the treated group (burned mice and injected with pediatric ADSC) from control mice (burned but not injected with cells). A comparative analysis between the two groups of age will be conducted that will be also compared to data collected with adult ADSC.

To answer to the second part of this primary goal regarding to safety, the study will perform a long-term follow-up (1 yr) of burned mice injected with of ADSC, to obtain data in the animal after transplantation of cells and for further clinical study.

Complementary in vitro investigations still seems necessary to better understand the specificities of ADSC from pediatric origin and particularly to perform transcriptomic and epigenetic studies.

Eligibility criteria: INCLUSION CRITERIA:

* absence of tumor pathology, known systemic or chronic viral
* absence of long-term treatment
* signing informed consent form of persons exercising parental authority

  1st group (20 children):
* Between 0 and less than or equal to 1 year
* Weighing at least 1500 g at birth
* Age ≥ 37 weeks of amenorrhea

  2nd group (20 children)
* Older than 1 year to 10 years

EXCLUSION CRITERIA:

* Children whose age is above 10 years
* premature babies with birth weight under 1500 grams
* Any child with a tumor pathology, a systemic disease, or whose serology (viral) would be known as positive (HIV 1 and 2, hepatitis B, C, ...).
* Any child following a long term treatment.

Primary outcomes:
measure: Efficacity of treatment as assessed by surface healed skin (cm2) in animal model
timeFrame: 1 month after injection
measure: Efficacity of treatment as assessed by surface healed skin (cm2) in animal model
timeFrame: 1 year after injection
measure: Security as assessed by absence of tumorigenicity at injection site in animal model
timeFrame: 1 month after injection
measure: Security as assessed by absence of tumorigenicity at injection site in animal model
timeFrame: 1 year after injection
Secondary outcomes:
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU de Toulouse-Purpan
Study officials:
affiliation: Chirurgie pédiatrique - Hôpital des enfants
name: Philippe GALINIER, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abbo O, Taurand M, Monsarrat P, Raymond I, Arnaud E, De Barros S, Auriol F, Galinier P, Casteilla L, Planat-Benard V. Comparison between pediatric and adult adipose mesenchymal stromal cells. Cytotherapy. 2017 Mar;19(3):395-407. doi: 10.1016/j.jcyt.2016.11.012. Epub 2016 Dec 28.