Please read carefully

For Patient Reference

Vascular Regeneration Therapy for Lower
Limb Ischemia by Autologous Peripheral
Blood
CD34 Positive Cell Transplantation

Explanatory Document and Consent FormShonan Kamakura General Hospital Ver.2.2
Date of Creation：March 30, 2023
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TABLE OF CONTENTS
1.

INTRODUCTION ····················································································· 3

2.

EXPLANATION OF REGENERATIVE THERAPY ·········································· 43.

METHOD OF REGENERATIVE TREATMENT ·············································· 54.

PLANNED DURATION OF TREATMENT ··················································· 17

5.

ANTICIPATED BENEFITS AND RISKS ····················································· 176.

OTHER TREATMENTS FOR CRITICAL LOWER LIMB ISCHEMIA ················ 24

7.

POTENTIAL HEALTH HAZARDS ····························································· 24

8.

PROTECTION OF PERSONAL INFORMATION ·········································· 25

9.

RECORDS AND SAMPLE HANDLING ······················································ 25

10. COST OF TREATMENT ·········································································· 26
11.

COMMUNICATION OF INFORMATION THAT INFLUENCES THE INTENTIONTO IMPLEMENT TREATMENT ································································ 27

12. DISCONTINUATION OF THERAPY ························································· 27
13. WITHDRAWAL OF CONSENT ································································· 28
14. FOLLOW-UP AFTER COMPLETION OF TREATMENT ································ 28
15. REQUESTS FOR YOUR COOPERATION ·················································· 28
16. HANDLING OF THE RESULTS ································································ 29
17. FOR INQUIRIES ···················································································· 30

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Date of Creation：March 30, 2023
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1.

Introduction

This document is an explanation of the regenerative therapy called "Lower
Limb Vascular Regeneration Therapy by Autologous Peripheral Blood CD34
Positive Cell Transplantation," which is being performed at our hospital.
Please listen to the doctor's explanation regarding this therapy and after
fully understanding the contents of this document, please decide whether or
not to undergo this therapy using your own free will. If you feel that you arewilling to undergo this treatment, please sign the "Consent Form".
Even if you decide to not undergo this particular therapy, you will not face
any disadvantages in finding or receiving other forms of treatment that you
will determine to be best for you.
Furthermore, even if you agree to undergo this therapy, you may stoptreatment at any time. In such cases, other treatments considered to be bestfor you will be provided, and you will not suffer any disadvantages.
The treatment plan for this regenerative therapy reviewed by the Certified
Special Committee for Regenerative Medicine (Shonan Kamakura General
Hospital Certified Committee for Regenerative Medicine see page 31 fordetails), which is accredited by the Ministry of Health, Labour and Welfare, toensure that there are no problems in terms of the protection of human rights,
the safety of the participants, and the scientific nature of the regenerative
therapy in accordance with the laws established by the government (Act on
Securing Safety of Regenerative Medicine, etc.) and related notifications.
Based on the results of the review, the plan was submitted to the Ministry of
Health, Labour and Welfare through the Regional Health and Welfare Bureau.
In addition, the plan was also approved by the Director of Shonan Kamakura
General Hospital.
If you wish, we will do our best to provide you with additional materials
regarding the plans for administration and treatment methods of thisregenerative therapy. We will also provide you with information about theeffects and conditions of this regenerative therapy. If you are interested insuch materials, please contact the listed in the contact information on page
30.

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2.

Explanation of Regenerative Therapy

2.1.

About your diseaseYour disease has been diagnosed as critical limb ischemia.
This disease is a chronic condition with symptoms such as pain in the lower
limbs and ulceration/necrosis of the skin.

2.2.

Conventional treatment methods

To date, the following treatments have been used to treat critical limb
ischemia.

◇◆Conventional treatment◆◇
１ ） Medical treatment: vasodilators and antiplatelet agents (drugs thatprevent the formation of blood clots)２）Angioplasty: Balloon dilation (widening of blood vessels with balloons)and stenting (placement of a metal tube in a narrowed or blocked bloodvessel)３）Surgical bypass surgery: surgery using arterial or venous grafts (surgery
to improve blood flow by connecting another blood vessel (called agraft) to a narrowed or blocked blood vessel)４）Gene therapy: Intramuscular administration of a gene that promotes
angiogenesis at the site of ischemia.

The above treatments are effective for patients with mild symptoms, but forpatients with severe cases such as yourself, treatment 1) cannot be expected
to show sufficient effects, and treatments 2) and 3) are also deemed
insufficient due to surgical limits regarding the maximum number of bloodvessels that can undergo operation. Additionally, these treatments cannot be
performed in case of the occlusion of small peripheral vessels. As for 4), thistreatment became covered by insurance in September 2019, but its approval
is subject to conditions and time limits.

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2.3.

About the method of regenerative therapy

This new method of regenerative therapy aims to treat critical limb ischemia
by regenerating blood vessels using your own cells.
◇◆New treatments◆◇
This is a treatment to regenerate blood vessels by removing cells fromthe patient's blood, isolating the cells that produce blood vessels(autologous peripheral blood CD34 positive cells) from the rest of thecells and transplanting them into the lower limbs.
This type of cell transplantation therapy is called cell therapy. The CD34
positive cells to be transplanted are undifferentiated cells found in bonemarrow and blood, and are thought to have the ability to become bloodvessel-forming cells when transplanted into organs or tissues with impaired
blood flow.
Several studies have been conducted on the improvement of critical limb
ischemia by transplantation of CD34 positive cells, and animal studies as wellas actual patient studies have shown that the transplantation of CD34
positive cells creates new blood vessels, which may be effective in preventing
the progression of necrosis of lower limb muscles and eventual lower limb
amputation.
However, this treatment may cause side effects due to the medication usedduring cell harvesting, as well as side effects from the manipulation of cell
harvesting (apheresis) (see 5. Anticipated benefits and risks).

2.4.

About this regenerative therapy

This regenerative therapy will provide transplantation of the patient's own
peripheral blood CD34 positive cells to patients with critical limb ischemia(peripheral artery disease) whose symptoms have not been improved byconventional medical therapy, angioplasty, surgical bypass surgery. After thetreatment, we will confirm the efficacy of the treatment and the safety of thepatient for up to 24 weeks.

3.

Method of Regenerative Treatment

3.1.

Eligible patients
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Patients who meet all of the following criteria 1)-6) are eligible.
1）Patients with lower limb ischemia (peripheral artery disease) who havean occlusion or significant stenosis (internal diameter stenosis rate of
70% or more) confirmed by lower limb arteriography, CT angiography,or MRA, or those who are judged to have pain or ulcer/ necrosis due tofoot ischemia even if no occlusion or significant stenosis is confirmed bythese imaging diagnostics.
2）Patients with lower limb ischemia whose pain at rest or
ulceration/necrosis has appeared more than 12 weeks prior to thedate of consent.
3）Those who feel pain in the lower limbs at rest due to ischemia of thelower limbs, or those who have ulcers or necrosis of the lower limbs
and have no other effective means of wound treatment.
4）Those for whom angioplasty or bypass surgery is not administered (i.e.,cases where stenosis is too diffuse or in small peripheral arteries,
making angioplasty or bypass surgery inappropriate), or those who areseriously ill and fall under criterion 3) (above) in spite of having received
these prior treatments.
5）Aged 20 years or older at the time of consent.
6）Those who can provide written consent themselves.
However, those who meet any of the following conditions are not eligible.
1）Patients with severely impaired heart function.
2）Those who have a history of serious hypersensitivity or side effects tomedications or reagent components used in this regenerative therapy.
3）Patients with a malignant tumor(s) or a history of a malignant tumor(s)within the past 5 years※1
4）Patients with diabetic proliferative retinopathy (neo-Fukuda
classification BII to BⅤ)
5）Patients with unstable angina pectoris or myocardial infarction, or
patients who have suffered the onset of a stroke within the past 12
weeks.
6）Patients with leukemia, myeloproliferative disorders, myelodysplastic
syndromes, or sickle cell disease.
7）Patients with liver cirrhosis.
8）Patients with complications concerning, or a history of interstitial
pneumonia.
9）Patients with cerebral artery aneurysms that require treatment.
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C virus, or human immunodeficiency virus (HIV).
11） Patients with rest pain, ulceration, or necrosis of the lower extremities
due to spinal canal stenosis, joint diseases, vasculitis, etc. (Even if apatient has these diseases, it is not a disqualifying criterion if the rest
pain or ulceration necrosis is determined to be caused by ischemia ofthe lower limbs)
12） Patients with osteomyelitis, osteonecrosis, exposure of bone or tendon
due to ulceration or necrosis, or complications of sepsis, for whommajor amputation of the lower extremity (amputation at the ankle joint
or more centrally) is inevitable regardless of the success of vascularregeneration therapy.
13） Pregnant women, lactating women, women who may be pregnant, andwomen who plan to become pregnant by the end of the treatment
period.
14） Those who are participating in other clinical trials or clinical studies.
15） Those who are otherwise judged by the assigned physician to beineligible for participation in this regeneration therapy.
※1 In the search for malignant tumors, the following tests are performed:
CT scan (chest, abdomen), head MRI (if the doctor in charge determines thatan MRI is not appropriate, other tests such as a CT or angiography may besubstituted), urine cytology (only for those who maintainurine), humanhemoglobin test via stool samples, colonoscopy (only for those who arepositive in the stool test; if the colonoscopy shows no abnormalities, an uppergastrointestinal endoscopy will be performed), and serum PSA (men only),cervical Papanicolaou test (women only), and breast examination andmammography (women only).

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3.2.

Treatment Schedule

First, you will be tested to determine if you are an eligible candidate for thistreatment. If it is determined that you are eligible, you will be enrolled in thetreatment, and treatment will begin within four weeks from the date ofenrollment.
3.2.1. Attendance at regular intervals
The planned period of participation is the treatment period (approximately
one week from the start of G-CSF [granulocyte colony-stimulating factor]
preparation administration to cell therapy) and the observation period (24weeks) for the progress of the treatment. Cell harvesting (apheresis) is
performed on the fifth day after the start of treatment (start of G-CSF
administration), cell transplantation is performed on the next day (the sixthday), and tests and observations are performed on the next day oftransplantation (the seventh day), as well as one week after transplantation.
Therefore, patients will be hospitalized for about two weeks from the day
before the start of treatment to one week after the transplantation. The restof the time, the patient will be seen as an outpatient.
In addition, the period from the start of treatment to the end of theobservation period is approximately six months after registration.
For details regarding the test items and schedule at each point, please refer
to "Main test items and schedule" on page 14.
A diagram of the process from consent to registration, cell therapy,
observation, etc. is shown on the next page.
3.2.2. What takes place before registration◆Screening phase (before registration)
After you agree to undergo this treatment, we will assess your general
health conditions and check for the presence of malignant tumors before
performing the cell transplantation. Other tests will be conducted todetermine whether or not you are a suitable candidate for this treatment.
If any of the same, required medical tests were performed recently before
you consented to this treatment, we may use their results in order to reduce
the number of tests scheduled.
Within 16 weeks prior to registration: Background interview (gender dateof birth, date of consent, age on date of consent, information on
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lower limb ischemic disease, medical complications/history, smoking
history, dialysis information), lower limb angiography or CT
angiography or MRA, head MRA* chest and abdominal CT,
malignancy search (chest and abdominal CT, cerebral MRA*,
maintain urine cytology only for those who maintain urine, stool testcolonoscopy only for those who test positive in the stool test, serum
PSA only for male patients, cervical Papanicolaou test only forfemale patients, breast examination and mammography only forfemale patients,) ocular fundus test, and echocardiography.
※
If the physician in charge determines that MRI or MRA is not appropriate,
other tests such as CT or angiography may be substituted.
Within 2 weeks prior to registration ： Physical examination, lower limb
physiological function tests, blood tests, infectious disease tests,
electrocardiogram, evaluation of pain due to lower limb ischemia,
lower limb ulceration/necrosis findings, transplanted limb
information, pretreatment information, and minor amputation
schedule after registration.
Angiography, MRI, MRA, CT, etc. take about 1 to 2 hours each, including
waiting time. Lower limb physiological function tests take less than one hour.
If various tests are performed at a hospital(s) other than our hospital (suchas your regular hospital), the results of those tests can be used.

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3.2.3. What happens from cell transplantation phase - after transplantation◆Treatment period① Treatment to deliver bone marrow cells to blood (subcutaneous injectionof G-CSF preparation.)
CD34 positive cells are usually found in large numbers in bone marrow,and only a small number in the blood. G-CSF, a medication that helps
deliver the necessary amount of CD34 positive cells from the bonemarrow into your bloodstream, is injected subcutaneously at a dose of
400 µg/m2 once a day for up to 5 days. The dose will be administered on
the same day that hematological test and blood biochemistry test are
performed and after the results are confirmed.
The G-CSF preparation also increases the number of neutrophils (a typeof white blood cell) in the blood. If the white blood cell count reaches
75,000/µL or higher, the administration of the G-CSF preparation would
be stopped and apheresis would be performed on the same day. In suchcases, the administration period of the G-CSF preparation will be
shortened to less than 5 days.

② Procedure to collect mononuclear cells including CD34 positive cells from blood（Apheresis）
On the fifth day of G-CSF administration（or the day the white blood cellcount reaches 75,000/µL or higher）, “Apheresis” will be performed. To
collect sufficient number of cells needed for transplantation (mononuclear
cells), percutaneous catheter insertion into jugular or inguinal vein isnecessary. Then, blood will be drawn through catheter, and mononuclear
cells for transplantation will be separated using a cell separator. The otherblood components will be returned to your body. (The inserted catheter
will also be used as a route for fluid infusion. Catheter will be removed on
day 7 [the day after cell transplantation] otherwise specified).
During apheresis, blood pressure and electrocardiogram will bemonitored for your safety. Hematological tests will be performed justbefore the start and just after the end of apheresis, and blood biochemical
tests will be performed just after the end of apheresis.
The method of cell extraction （① Subcutaneous injection of G-CSF
preparation & ②Apheresis） described above has been established as a
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general method.
Please note that apheresis takes around 3 hours.
③ CD34 positive cells magnetic sorting
On the next day of “②Apheresis”, CD34 positive cells are separated
from mononuclear cells extracted during “②Apheresis” using a magnetic
cell separator＊.
If the purity, survival rate, and cell count of the isolated cells meet the
specified conditions, cell therapy is performed.
〔Guideline for transplanted cells〕
Purity：25％ or more
Survival rate：70％ or more
Cell count：1 x 105 per kg of body weight or
moreHowever, even if any of the rates are less than
the above values, cell transplantation can still be
performed with the patient’s consent.

Magnetic cell separator：Uses CliniMACS（Miltenyi Biotec）.

＊

This is a medical device that has not yet been approved in Japan, but it
was developed for the purpose of separating cells for hematopoietic
stem cell transplantation for leukemia patients, and its safety has been
approved in the United States, the European Union, South Korea,
Singapore, and a number of other countries.

④ Cell therapy（Transplantation）
The isolated cells （ CD34 positive cells ） are transplanted into thepatient's lower limbs by intramuscular injection. The amount of cellsuspension to be transplanted per site is 0.25 mL, and 40 sites aretransplanted per lower limb where transplantation therapy is performed.
The maximum number of cells to be transplanted is 2 x 106 cells (2 million
cells) per kg of body weight per day, regardless of whether the transplant
treatment is performed on one or both lower limbs.

In the case oftransplantation to both lower limbs, the timing of the transplantation may
be staggered and the cell therapy treatment for each lower limb may be
performed separately instead of transplanting the cells to both limbs atthe same time.

Also, if the number of CD34 positive cells collected is low,

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less than 1 x 105 cells per kilogram of body weight (100,000 cells perlimb), transplantation can still be performed with the patient's consent.
Anesthesia （ General anesthesia, transfer anesthesia, or surface
anesthesia） will be administered during the transplantation process inorder to relieve any pain during the procedure.
Please note that cell transplantation takes about 1-1.5 hours （ forunilateral affected limbs only） from the start of anesthesia to the end of
the transplantation.

Some of the isolated CD34 positive cells are also used for quality testingand storage.

Further tests may also be performed to examine thecharacteristics/conditions of the transplanted cells.

However, genetic

testing will be never performed.
◆Observation period
1 day, 7 days, and 24 weeks after transplantation, observation andexamination will be conducted to evaluate the safety of the patient andthe efficacy of the treatment.

When the observation is discontinued forany reason, an assessment of patient safety and feasible efficacy is also
made. For information regarding the discontinuation of therapy, pleaserefer to "12. Discontinuation of therapy.
24 weeks of medical examinations and tests can be completed in about
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half a day, so in principle it should be possible to make outpatient visits foryour appointments.

However, please note that it may take additional time

if you have to receive eye examinations.

It is also possible to implement

the program at a hospital other than our hospital (e.g., your primary careclinic).
For details regarding the test items and each's schedule, please refer to"Main Test Items and Schedule" on page 14.
If you have any questions about any of the tests, please contact yourdoctor.

Other medical procedures may be performed depending on your

medical conditions.
3.2.4. Main test items and schedule
The main test items and schedule are shown on the next page.
For hematological and biochemical tests, about 10 mL of blood will bedrawn at a time.

Also, before starting treatment, there will be a

coagulation system and infection test, and about 10 mL of blood will bedrawn separately for this purpose. Hematological and blood biochemical
tests will be performed a total of 12 times, beginning from the preregistration examination before the start of treatment, carrying throughthe period of G-CSF preparation administration, and continuing until theend of the 24-week observation period after cell transplantation.

Pleaseunderstand that the total amount of blood collected over a period of
about six months will be about 120 mL.

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Main test items and schedule〔Before registration～At the time of cell transplantation〕
Pre-registration test
Date of
tests
Test Items
Subject background
Lower limb
angiography※3

Within 16
weeks priortoregistration

Within 2
weeks priortoregistration

※4

○
※5

○

※6

○

○
○

Ocular fundus test○

Echocardiogram○※2

Abdominal echo

Electrocardiogram

Lower limb ischemia
severity classification
Severe degree ofpain due to lower
limb ischemia
Ulceration findings
Lower limb MRI
Transplanted limb

Celltransplantation○

Stool test

Lower limb
physiological
function test
Hematological test
and bloodbiochemistry test
Coagulation system
test
Infectious disease
test

Apheresis
performance※2○

Physical findings

G-CSF
administration○

Urine cytology
Lower or upper
endoscopy
MRI and MRAof head
Chest CT,
Abdominal CT
Malignant tumors※7
searchTreatment period※1

period

○

○

※8

○

※9

※9

○

○

※10

○

※11

○

○

○

○
○
○
※12

○

○
○
※13

○

○

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information
Concomitanttreatment andmedication
G-CSF preparation
administration
record○○○○Apheresis record○

Transplanted cell
information
Adverseevents/outcomes
Magnetic cell
separator
malfunction
Allowed test date

○

○

○
－

－

±0 days±0 days±0 days※1：Pre-registration test period: Previous test data collected prior to obtaining consent for thisprocedure will be used if additional consent is obtained from the patient.
※ 2 ： Patients suspected of having coronary artery disease based on electrocardiogram,echocardiogram, medical history, etc. will undergo a thorough examination using myocardial
scintigraphy, coronary CT, and/or coronary angiography, etc.
※3：This test is performed using direct angiography, CT angiography or MR angiography.
※4：This is only performed for patients who have urine output.
※5：A colonoscopy will be performed when the fecal hemoglobin test is positive. If the colonoscopyshows no abnormalities, an upper gastrointestinal endoscopy will be performed.
※6：For patients with contraindications or ineligibility for MRI or MRA, a CT or angiography, etc. will
be used instead.
※7：The following tests will be performed.
CT scan (chest, abdomen), MRI of head (for patients with contraindications or ineligibility for
MRI, a CT etc. will be used instead), urine cytology, fecal hemoglobin test, colonoscopy (onlywhen the fecal hemoglobin test is positive), serum PSA (only for male patients), Cervical
Papanicolaou test (only for female patients), breast exam and mammography (only for female
patients)※ 8 ： Abdominal echocardiography will be performed on either day 3 or 4 of the G-CSF
administration period.
※9：Only body temperature and weight will be measured.
※10：Test of HbA1c, glycohemoglobin (only for diabetic patients).
※11：Blood biochemistry tests will be performed only on days 1, 3, and 5.
※12：Evaluation of both limbs.
※13：This is performed only for patients belonging Rutherford Classification category 5 or 6.

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〔During the observation period〕（Observation schedule for each target limb）#
Inspection
periodInspection
Items

Period of observation
Day 1 after
transplantation

Day 7 after
transplantation

Lower limb
ischemia severity
classification
Severe degree ofpain due to lower
limb ischemia

Discontinued

24 Weeks
aftertransplantation
○

○

○

○

Ulceration findings○○

Lower limb
physiological
function test

○

○

※9

※9

Physical findings○○

Hematological test
and bloodbiochemistry test○○

Electrocardiogram
Ocular fundus
test
Concomitanttreatment andmedication

※14

※10

○

※10

○

○
※15

○

※15

○

○

○

○

○

±0 days±3 days±14 days－

Adverseevents/outcomes
Allowance ofinspection period＃： If both limbs have been affected and thereby treated separately with transplantation therapy, theobservation for each target limb will be performed according to each's own observation schedule as
described above..
※9：Only body temperature and weight will be measured.
※10：Test of HbA1c, glycohemoglobin (only for diabetic patients).
※14：If treatment is discontinued during the therapeutic period, safety tests and studies will be conducted at
the time of discontinuation. Tests for efficacy will also be conducted if possible.
※15：Only for diabetic patients.

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3.3.

Concomitant therapy and medications◆Contraindicated medications and treatments
The following treatments are prohibited within 24 weeks of celltransplantation as they may affect the evaluation of this treatment.
However, we do not limit the following treatments to those who show
intensified pain or ulceration after cell therapy, if they wish to do so.
・Other cell transplantation therapies
・Gene therapy
・Sympathetic ganglion block・Angioplasty of the lower extremities, bypass operation
・LDL apheresis
・Other medication from clinical trials and clinical trial equipment◆Limited medication
1) With a limited period of use(Your physician(s) may reduce the dose of or suspend the use of thefollowing medications depending on your condition.)・Warfarin Potassium（Product name：Warfarin etc.）

4.

Planned Duration of Treatment

This treatment will be conducted at one facility, Medical Corporation
Tokushukai Shonan Kamakura General Hospital.
The total duration of treatment will last approximately five years from thetime the treatment is approved for implementation.

5. Anticipated Benefits and Risks
5.1.

Anticipated benefits

Several clinical studies have been conducted on the effects of CD34
positive cell transplantation in patients with critical limb ischemia. It has beenreported that the treatment may be effective in reducing ulcers and necrosisof the lower limbs and preventing amputations of the lower limbs.
Transplantation of CD34 positive cells into patients with critical limb ischemia

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on maintenance hemodialysis, which is difficult to treat, may help create newblood vessels and improve pain, ulcers and necrosis of the lower limbs.

5.2. Anticipated risksYour doctor will also closely monitor you for any unfavorable symptoms orsigns (called adverse events) that occur after treatment.
If an adverse event occurs, you will be informed and appropriate action will
be taken accordingly. If necessary, treatment may be discontinued.
The following are examples of possible symptoms, which may vary frompatient to patient. Please contact your doctor if you notice any changes inyour physical condition.
1）Side effects of the G-CSF products used in this treatment
In this treatment, a G-CSF preparation is administered at 400 µg/m2.
Past reports show high frequency incidences where doses that wereadministered higher than 10 µg/kg (similar to this treatment's dose) wereaccompanied by bone pain, headache, and general malaise.
The following is what is described in the prescribing information of the GCSF products＜Serious side effects＞
Shock, Anaphylaxis （ Frequency unknown ） , interstitial pneumonia*1（Frequency: unknown）, acute respiratory distress syndrome*2（Frequency:
unknown ） , increased number of blasts （ Frequency unknown ） ,splenomegaly(Frequency unknown ), rupture of the spleen（Frequency:
unknown）, capillary leakage syndrome（0.01% of cases）, large vessel
vasculitis（inflammation of the aorta, common carotid artery, subclavian
artery, etc.）（Frequency unknown）＜Other side effects＞
Skin：(Frequency unknown) skin disorder with neutrophilic infiltration, painful
erythema, and fever（Sweet Syndrome, etc.）*3 (Less than 1%) rash,redness of skinMuscles and bones：(1%-less than 5%) bone pain, back pain, (Less than 1%)

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chest pain, joint pain, muscle pain, (Frequency: unknown) pain in extremity
Digestive organs：(Less than 1%) nausea and vomiting
Liver：(Less than 1-5%) increase in ALT (GPT), (Less than 1%) hepatic function
abnormal, increased AST (GOT)
Blood：(Frequency unknown) platelet decreased, leukocytosis
Kidney：(Frequency unknown) glomerulonephritis
Other：(Frequency unknown) Edema, (Higher than 5%) DH elevation, (1%-less than5%) fever, increased Al-P(Less than 1%), headache, fatigue, palpitations,elevated uric acid, elevated serum creatinine, elevated CRP*1interstitial pneumonia：Inflammation of the interstitial tissue of the lungs causes
symptoms such as coughing, shortness of breath, and fever.

*2

Acute respiratory distress syndrome：This is an acute lung injury with a variety of
causes. Symptoms include difficulty breathing and hypoxia.

*3

Skin disorder with neutrophilic infiltration, painful erythema, and fever （Sweet
Syndrome, etc.）：This is a type of skin condition that is accompanied by redness,pain, itching and burning.

2）Side effects of apheresis
Side effects that may be caused by apheresis are as follows
platelet decreased （ higher than 50 ％ ） , general malaise （ about 30 ％ ）,numbness of extremities （ citric acid poisoning by ACD solution used as
anticoagulant）, vomiting vasovagal reflex*4, dehydration, bradycardia, ascites
accumulation*4

Vomiting vasovagal reflex：Symptoms such as dizziness, nausea, and vomiting may
occur due to anxiety and fear of blood sampling and injection.

Vasovagal reflex is very rare, but in severe cases it can lead to bradycardia,
loss of consciousness, and even cardiac arrest. For the safety of the patient,
we will monitor the patient with an electrocardiogram during apheresis andbe prepared to respond in the case of an emergency.
3）Side effects of cell transplantation (CD34 positive cell transplantation)
No side effects have been reported with autologous CD34 positive cell
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19

transplantation. However, possible risks include the following:① Risk of bacterial or viral infection of isolated transplanted cells, and thetransplantation of such already-infected cells to you
Transplant cells are separated by aseptic manipulation, but the risk ofbacterial (e.g., syphilis, tuberculosis), viral (e.g., hepatitis B, hepatitis C, HIV), or
mycoplasma infection of the cells cannot be completely ruled out.
To ensure your safety, a portion of the cells obtained during separation (CD34
negative cells) will be tested for the presence of these infections. （The resultsof the test will be known after the cell transplantation.） If the test confirms
any infection, a specialist will provide the appropriate treatment（for example,
the administration of globulin products, antiviral drugs, antibiotics, etc.）.
② Risks associated with drugs used during cell separation.
〔Risks depending on the antibody used〕
When separating the cells, it is necessary to use antibodies made frommouse proteins, and very small amounts of mouse proteins may enter yourbody along with the transplanted cells. As a result, your body may produce
antibodies against the mouse proteins. Please note that if antibodies to themouse protein are produced in the body, allergic reactions and anaphylactic
symptoms*5 may occur, and there may be restrictions on future treatments
using similar mouse proteins.
*5allergic reactions and anaphylactic symptoms：The most common symptomsof allergic reactions are skin symptoms such as hives, redness, and itching. Other
symptoms include respiratory symptoms such as sneezing, coughing, wheezing,
and breathlessness; mucosal symptoms such as itchy eyes, swelling, and swollen
lips; gastrointestinal symptoms such as abdominal pain and vomiting; circulatory
symptoms such as low blood pressure. Anaphylaxis is the rapid onset of these
multiple symptoms throughout the body.

〔Risks arising from the manufacturing process of the antibodies used〕
In the manufacturing process of the antibody used to isolate CD34 positive
cells, no components of human or animal origin are used other than themouse-derived cells that produce the antibody.

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In the production of antibodies using mouse-derived cells, safety measures
have been taken to reduce the risks of infection. However, when using of
biologically-derived raw materials, the risk of infectious diseases cannot becompletely eliminated.
〔Risk depending on the human serum albumin used〕
Human serum albumin, which is commercially available as medicine, is usedduring the isolation of CD34 positive cells. Therefore, allergic reactions tohuman serum albumin and anaphylactic symptoms may occur.
This human serum albumin is a medicine derived from domestic humanblood components, and has been tested negative for hepatitis B virus,
hepatitis C virus, and human immunodeficiency virus in infectious diseaserelated tests. Although the risk of infection cannot be completely eliminated,safety measures are in place to prevent associated risks during its production.
③ Risks associated with general anesthesia during transplantation
The possible side effects of general anesthesia when transplanting cells into
the muscles of the lower limb are as follows:
Sore throat, hoarseness, nausea, headache, damage to vital organs (brain,heart, lungs, liver, kidneys, etc.), abnormal reactions to medications (allergies,
malignant hyperthermia, etc.), teeth falling out, teeth breaking, nerve
damage (numbness, paralysis)4）Other information concerning side effects
According to the Donor Adverse Event Report of the Japan Society for
Hematopoietic Cell Transplantation, there have been no reports of donor
deaths in Japan so far, but there have been 8 deaths overseas after
granulocyte-stimulating factor injection and apheresis administered to stem
cell donors for patients with blood disorders （ as of November 2014 ） .
However, the relationship between death and the procedure is not clear. In
addition, in a study of 1,780 donors who had been followed up for five years
out of 3,264 donors registered between April 2000 and March 2005 in the
Peripheral Hematopoietic Stem Cell Donor Follow-up Project for Blood
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Relatives

conducted

by

the

Japan

Societyfor

Hematopoietic

Cell

Transplantation, 12 persons (0.7%) developed nonhematologic tumors and1 person (0.06%) developed hematologic tumors. In addition, one donor(0.06%) developed a hematologic tumor, but a causal relationship toperipheral blood stem cell donation could not be denied but not clarified(reported in August 2010). In this regenerative therapy, the patient will
undergo the same procedure as the donor mentioned above.
In addition, the intravenous injection of CD34 positive cells obtained fromthe patient's own blood has been used for about 20 years in the treatmentof blood diseases and cancer. In a clinical trial for the treatment of nonHodgkin's lymphoma, two cases of pneumonia (4.9%) and one case ofvomiting (2.4%) were reported as side effects after CD34-positive celltransplantation,

but

the

symptoms

disappeared

withappropriate

administration of the drug.
In the domestic clinical trials conducted by the company in charge of thedevelopment of the CD34 positive cell isolation device, adverse reactions(including abnormal changes in clinical laboratory values) were reported in 16(35.6%) persons of non-Hodgkin's lymphoma out of 45 persons (41 personsof non-Hodgkin's lymphoma and 4 persons of breast cancer).
The most common adverse reactions were 8 cases (17.8%) of increased Creactive protein＊１, 8 cases (17.8%)#1 of cytomegalovirus infection＊２, 7 cases(15.6%)#2 of decreased lymphocyte count, fever in 3 cases (6.7%), andpneumonia in 3 cases (6.7%). In these trials, chemotherapy as an anticancer
drug was used in combination.
However, since this regenerative therapy targets a different disease fromthe above and does not involve the use of anticancer drugs, this information
regarding side effects does not directly apply to the regenerative therapy at
hand.

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5% and more

Less than 5%

Digestivenone
organsRespiratorynone
organsabdominal enlargement, vomiting

Skin

none

dermatitis, bullous dermatitis, pruritus

Urinaryorgansnone

proteinuria, hematuria, increased
creatinine in blood

cough, pleurisy, rhinorrhea, increased
sputum production, upper respiratory
tract inflammation, hypoxia

decreased white blood cell count,decreased neutrophil count, decreasedBlooddecreased lymphocyte
platelet count, decreased hemoglobin,count*1）
increased white blood cell count,increased neutrophil countincreased C-reactive

Other

protein, cytomegalovirus
infection*2）, fever,herpes simplex, shingles, cystitis

pneumonia#1）

Including 1 case of lymphopenia#2）

Including 2 cases of cytomegalovirus antigen positive＊1

C-reactive protein：A protein that appears in the blood when there is an inflammatory
reaction or tissue destruction in the body.

＊2

Cytomegalovirus infection：Cytomegalovirus is a member of the herpes virus family, andalthough it rarely causes symptoms in healthy people, it can cause a variety ofsymptoms such as fatigue, fever, sore throat, swollen lymph nodes in the neck,enlargement of the liver and spleen, and abnormal liver function in people withweakened immune systems.

5) Non-efficacy and inapplicability
Improvement of critical limb ischemia may not be provided by this celltransplantation therapy. If you have any symptoms that concern you after thestart of treatment, please do not hesitate to consult your doctor at any timeabout anything. We will do as many tests and treatments as possible ifnecessary. In such cases, we may ask for your cooperation in investigating thecause(s) of the symptom(s).

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6. Other Treatments for Critical Lower Limb Ischemia
Other treatments for critical lower limb ischemia include angioplasty, bypass
surgery, and treatment with peripheral vasopressors. However, angioplasty
and bypass surgery may not be sufficiently effective due to surgical limits
regarding the maximum number of blood vessels that can undergo operation,
and also due to the inability of the procedures to treat occlusions of peripheral
small blood vessels. Gene therapy, another alternative, has not yet beenstudied in comparison to this treatment, so it is still unknown which treatment
would be more effective. (Please refer to “2.2. Conventional treatment
methods”).
Finally, it is important to note that patients who undergo treatment using
CD34 positive cell transplantation can continue to receive medication(s) they
have been taking before this treatment.

7. Potential Health Hazards
This treatment is scientifically planned and carefully administered. However,
if you experience any side effects or other health problems at any time fromthe start of treatment to the post-treatment observation period, pleasecontact your doctor immediately. Your physician will provide you withappropriate medical care and treatment.
Specific measures to address health hazards are as follows:● We will provide treatment and other necessary measures for healthdamages.
●Medical expenses will be paid by the hospital.
●Compensation for death and disability will be paid in accordance with therules of the hospital's insurance policy. However, no monetarycompensation will be paid for other health damages.
Please note that the following cases are not eligible for compensation:● If the health problem turns out to be unrelated to this treatment.
● If the health hazard was caused by your intentional or negligent act.

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● If cell transplantation is not effective.

8. Protection of Personal Information
All hospital staff, including doctors, nurses, and pharmacists, are obligatedto maintain confidentiality regarding what they learn in the course of theirduties during normal medical treatments, and the same obligation ofconfidentiality applies to this treatment.
The handling of personal information is reviewed in advance by a Certified
special committee for regenerative medicine.

When the compiled information

is published in academic conferences or medical journals, care is taken to
ensure that individuals are not identified.
As such, your personal information is strictly controlled, so there is no need
to worry about your own or your family's personal information being leaked toa third party by undergoing this treatment.
By signing this consent form, you agree to the provision of information toorganizations other than this hospital*, the publication of results, and theinspection of medical records.
*

organizations other than this hospital ： Certified special committee forregenerative medicine and the Ministry of Health, Labor and Welfare and its
related staff.

9.

Records and Sample Handling

9.1.

Use, storage, and disposal of samples and information

The record of this treatment will be kept for 10 years after the end of thetreatment and some of your samples(cells) will be kept for 5 years. In case of
infection or other problems, the cells may be used to investigate the cause of
the infection, but no genetic tests or other tests unrelated to the treatment
will be performed. We may also investigate the causes of side effects andother problems that occur in patients after transplantation. When disposingof these records, we will shred or incinerate them to prevent the leakage of
personal information.
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The cells will be anonymized (then a way that attached a registration
number that is coded in a format that does not identify the individual. andstored within our hospital. At the end of the storage period, the cells will bedisposed of appropriately as medical waste.
When records are destroyed at the end of the retention period for this study,
they will be shredded or incinerated, taking care to protect the patient's
personal information.

9.2.

Secondary use of information

The information collected in this treatment may be used for secondary
purposes for analysis in the future, but this will be done only after a newresearch plan is prepared and approved by the Research Ethics Review
Committee.

10. Cost of Treatment
By this treatment, the following expenses will be incurred: hospitalization
expenses during the treatment period after the start date of G-CSF
administration; drug, medical material, and laboratory expenses during G-CSF
administration,

apheresis,

CD34-positivecellisolation,

and

cell

transplantation; hospitalization expenses for post-transplant examinations*
during the observation period (1 day, 7 days, and 24 weeks) and laboratory
expenses, etc. The standard co-payment amount is approximately 6.6 million
yen with consumption tax (the same hereinafter). The patient will also be
responsible for the cost of extra bedding, as well as any other expenses
incurred at his or her request.
If you wish to have a pre-registration examination at our hospital, themaximum amount will be 220,000 yen for the examination within 16 weeks
prior to the registration. The maximum amount will be 88,000 yen for theexamination within 2 weeks prior to the registration. In addition, hospitalization
expenses for the number of days required for the examination will be charged.
※

The day of transplantation is considered day 0.

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11. Communication of Information that Influences the
Intention to Implement Treatment
During the observation period after the start of treatment, your doctor willpromptly inform you of any new information that may affect your decision tocontinue undergoing treatment. At that time, you will be asked to reconsider
whether you wish to continue treatment or not, and you may cancel thetreatment.

12. Discontinuation of therapyYour doctor may ask you to stop the treatment after you have agreed to it
and/or after it has already started.
◆Reasons for discontinuation related to the individual patient's condition:1）When it is difficult to continue treatment due to illness, etc.
2）In the event that you request discontinuation (withdrawal of consent)
after giving consent.
3）In case of death.
4）If, after enrollment, it is found that the conditions for implementing thetreatment are not met.
5）If your post-transplant observation cannot be continued due toreasons such as hospital transfer.
6）If the transplantation could not be performed due to malfunction ofequipment, deterioration of your condition, or if the cells collected are
not suitable for transplantation.
7）Failure to start cell therapy within 4 weeks of enrollment.
8）In other cases where the person in charge of the treatment or yourdoctor judges that the treatment cannot be continued.
◆Reasons for discontinuation related to overall treatment:
1）If it is judged that there is a problem with the safety or effectiveness ofthe treatment.
2）If it is determined that the continuation of treatment is no longer
meaningful during the course of treatment.
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27

3）When instructed by the hospital director or the Ministry of Health,
Labor and Welfare to discontinue treatment.
If you cancel the treatment midway, we will ask you to undergo an
examination to check your health status for your safety. We appreciate yourcooperation.
Finally, it is important to note that once the CD34 positive cells aretransplanted during this treatment, the procedure cannot be undone and theycannot be removed.

13. Withdrawal of Consent
Once you have given your consent to this treatment, you may withdraw yourconsent at any time. If you feel that you want to cancel the treatment, pleasetell your doctor at any time. Even if you do withdraw your consent, you will
not be treated unfavorably.
The data collected from the time you agree to the treatment until you cancel
the treatment will be treated as treatment data. If you do not want your data
to be used, please inform your doctor or other health care provider.

14. Follow-up after Completion of Treatment
Adverse events observed during the course of this treatment will befollowed up with periodic health checks as frequently as possible until
improvement or stabilization, and safety information will be collected. If any
sort of infection is suspected, the patient will be retested every 3 months andfollowed up until diagnosed as negative. This information will be stored in thesame manner as the data during treatment.

15. Requests for Your Cooperation
If you agree to undergo this treatment, we kindly ask that you pleaseobserve the following:
1） Please come to the hospital according to your schedule. If you are
Shonan Kamakura General Hospital Ver.2.2
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28

unable to come to the hospital according to schedule for any reason,
please inform your doctor as soon as possible.
2） If you are receiving treatment for other illnesses etc. from a doctor
other than your own, please be sure to inform your doctor of this.
Please also let us know if you are taking any medication(s) prescribedby another doctor or purchased at a pharmacy. If there are anychanges in the type or dosage of the medication(s) you are taking,please contact your doctor as far in advance as possible.
3） During the post-treatment observation period, if you wish to seeanother doctor for a cold etc., please consult with your doctor as far
in advance as possible. Also, please be sure to let the new doctor
know that you are also participating in this treatment.
4） There is no information yet on the safety of G-CSF products during
pregnancy and lactation. Women who are pregnant, lactating, or may
become pregnant should not receive this treatment. Women
receiving this treatment should also be advised not to become
pregnant during the observation period following the start oftreatment.
5） Please follow the instructions of the hospital staff when undergoing
medical examinations and measures.
Please note that your doctor may ask you to stop the treatment if you do
not follow the above instructions.

16. Handling of the Results
The results of this treatment may lead to some new insights. Any patent orother intellectual property rights (patent rights) that may arise will belong to
the medical institution that participated in the treatment or to the treating
physicians. This does not refer to the data provided, rather to the new ideasthat emerged as a result of the treatment as well as the application of theresults by the treating physicians. Therefore, the patient right belongs to the
medical institution or treating physicians who participated in the treatment.
Patients may not claim any financial benefits from the patent right.

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29

17. For Inquiries
If you have any concerns or questions about this treatment, or if you noticeanything unusual, please do not hesitate to contact your doctor or the
consultation desk at any time.

MedicalInstitutions andAdministrators

Medical Corporation okushukai
Shonan Kamakura General Hospital
Director Shuzo Kobayashi
Address: 1370-1 Okamoto, Kamakura, Kanagawa
247-8533, Japan
Phone: 0467-46-1717

Department
Chargein Regenerative Medicine and Kidney Disease andTransplant Center

PhysicianResponsible
Treatment

for Name of Physician：Takayasu Ohtake M.D.

AttendingPhysicianName of Physicians ： Sumi Hidaka M.D., Kunihiro
Ishioka M.D., Yasuhiro Mochida M.D. Machiko Oka
M.D., Ayaka Mitomo M.D.
Contact：Shonan Kamakura General Hospital
Phone：0467-46-1717

Consultation
Service

Contact: Shonan Kamakura General Hospital
Regenerative Medicine,or Kidney Disease andTransplant Center
Phone：0467-46-1717
Physicians : Takayasu Ohtake M.D.
Yasuhiro Mochida M.D.,

Service for
Medical travel
supportContact: International Department, Tokushukai
Medical Group
Phone：0467-46-9931 FAX : 0467-46-9932

company

Person in charge : Masaki Watanabe

Emergency
Contact during Contact: Shonan Kamakura General Hospital
Eveningand Phone：0467-46-1717
Holidays

Shonan Kamakura General Hospital Ver.2.2
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30

If you have any complaints, please contact the Clinical Research Center at
Shonan Kamakura General Hospital (0467-46-1717).
In addition, please refer to the following website for the list of the committee
members, committee rules, outline of committee meetings, and otherinformation pertaining to the. Certified Committee for Regenerative Medicine
Complaints and inquiries are also accepted at the following e-mail address.
Name of Certified Review Shonan Kamakura General Hospital Certified
Board

Committee for Regenerative Medicine

Accreditation Number ofNA8150013
the Certified Committee
Address1370-1 Okamoto, Kamakura, Kanagawa

Department in Charge

Shonan Kamakura General Hospital Certified
Committee for Regenerative Medicine Secretariat

Phone
Number
Department in Chargeof

FAX
Number
Department in Charge

of

Email
Address
Department in ChargeofWebsite03-3265-4804
03-3263-4802
rm_committee2@shonankamakura.or.jp
https://www.shonankamakura.or.jp/about/spregeneration-medicine/

The above is the explanation of the contents of this therapy. If you
understand and agree to this treatment, please sign the following consent
forms.

Shonan Kamakura General Hospital Ver.2.2
Date of Creation：March 30, 2023
31

For Hospital

Consent form

To: Director of Medical Corporation Tokushukai Shonan Kamakura General
Hospital

１．Consent Form for Cell Collection
Name of treatment： Vascular Regeneration Therapy for Lower Limb Ischemia
by Autologous Peripheral Blood CD34 Positive Cell Transplantation□

Introduction□ About the treatment□ Other treatments for critical limb ischemia□ How to do this treatment□□ Anticipated benefits and risks

Protection of personal information□ Cost of treatment□□ Communication of information that influences□ Retention and disposal of records

the intention to implement treatment

In case of health hazards
and samples□ Withdrawal of consent□ Discontinuation of treatment□ Requests for your cooperation□□ Contact information

Follow-up after completion of
the treatment□

Management of treatment results

I received a full explanation of the above items in written form. I understandthe details of this treatment and agree to have my cells collected. However, it
should be noted that consent may be withdrawn prior to the cell collection.
Date：_______________
Signature：□ I have received the explanation document and consent form (copy).
The above treatment was explained based on the explanation document.
Date：_______________
Explaining Physician： Department of
Signature：
Date：_______________
Attending Coordinator Department of
Signature：

Shonan Kamakura General Hospital Ver.2.2
Date of Creation：March 30, 2023
32

Consent form

For Patient

To: Director of Medical Corporation Tokushukai Shonan Kamakura General
Hospital

１．Consent Form for Cell Collection
Name of treatment： Vascular Regeneration Therapy for Lower Limb Ischemia
by Autologous Peripheral Blood CD34 Positive Cell Transplantation□

Introduction□ About the treatment□ Other treatments for critical limb ischemia□ How to do this treatment□□ Anticipated benefits and risks

Protection of personal information□ Cost of treatment□□ Communication of information that influences□ Retention and disposal of records

the intention to implement treatment

In case of health hazards
and samples□ Withdrawal of consent□ Discontinuation of treatment□ Requests for your cooperation□□ Contact information

Follow-up after completion of
the treatment□

Management of treatment results

I received a full explanation of the above items in written form. I understandthe details of this treatment and agree to have my cells collected. However, it
should be noted that consent may be withdrawn prior to the cell collection.
Date：_______________
Signature：□ I have received the explanation document and consent form (copy).
The above treatment was explained based on the explanation document.
Date：_______________
Explaining Physician： Department of
Signature：
Date：_______________
Attending Coordinator： Department of
Signature：

Shonan Kamakura General Hospital Ver.2.2
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33

For Hospital

Consent form

To: Director of Medical Corporation Tokushukai Shonan Kamakura General
Hospital

２. Consent Form for Cell Transplantation Treatment
Name of treatment： Vascular Regeneration Therapy for Lower Limb Ischemia
by Autologous Peripheral Blood CD34 Positive Cell Transplantation□

Introduction□ About the treatment□ Other treatments for critical limb ischemia□ How to do this treatment□□ Anticipated benefits and risks

Protection of personal information□ Cost of treatment□□ Communication of information that influences□ Retention and disposal of records

the intention to implement treatment

In case of health hazards
and samples□ Withdrawal of consent□ Discontinuation of treatment□ Requests for your cooperation□□ Contact information

Follow-up after completion of
the treatment□

Management of treatment results

I received a full explanation of the above items in written form. I understandthe details of this treatment and agree to have my cells collected. However, it
should be noted that consent may be withdrawn prior to the cell collection.
Date：_______________
Signature：□ I have received the explanation document and consent form (copy).
The above treatment was explained based on the explanation document.
Date：_______________
Explaining Physician： Department of
Signature：
Date：_______________
Attending Coordinator： Department of
Signature：

Shonan Kamakura General Hospital Ver.2.2
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34

Consent form

For Patient

To: Director of Medical Corporation Tokushukai Shonan Kamakura General
Hospital

２. Consent Form for Cell Transplantation Treatment
Name of treatment：Vascular Regeneration Therapy for Lower Limb Ischemia
by Autologous Peripheral Blood CD34 Positive Cell Transplantation□

Introduction□ About the treatment□ Other treatments for critical limb ischemia□ How to do this treatment□□ Anticipated benefits and risks

Protection of personal information□ Cost of treatment□□ Communication of information that influences□ Retention and disposal of records

the intention to implement treatment

In case of health hazards
and samples□ Withdrawal of consent□ Discontinuation of treatment□ Requests for your cooperation□□ Contact information

Follow-up after completion of
the treatment□

Management of treatment results

I received a full explanation of the above items in written form. I understandthe details of this treatment and agree to have my cells collected. However, it
should be noted that consent may be withdrawn prior to the cell collection.
Date：_______________
Signature：□ I have received the explanation document and consent form (copy).
The above treatment was explained based on the explanation document.
Date：_______________
Explaining Physician： Department of
Signature：
Date：_______________

Attending Coordinator：

Department of
Signature：

Shonan Kamakura General Hospital Ver.2.2
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35

For Hospital

Consent Withdrawal Form
To: Director of Medical Corporation Tokushukai Shonan Kamakura General
Hospital

Name of treatment： Vascular Regeneration Therapy for Lower Limb Ischemia
by Autologous Peripheral Blood CD34 Positive Cell Transplantation

I agreed to undergo the treatment, but I withdraw my consent.
□I have received the consent withdrawal form (copy).

Date：_______________

Signature：

Signature of the representative※：_______________（Relationship:）※

When the person's intention to withdraw consent cannot be confirmed.

Date of confirmation by physician
or person in charge of the treatment：

Signature of confirmation by physician
or person in charge of the treatment：

Shonan Kamakura General Hospital Ver.2.2
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36

For Patient

Consent Withdrawal FormTo:

Director of Medical Corporation Tokushukai Shonan Kamakura General

Hospital

Name of treatment： Vascular Regeneration Therapy for Lower Limb Ischemia
by Autologous Peripheral Blood CD34 Positive Cell Transplantation

I agreed to undergo the treatment, but I withdraw my consent.
□I have received the consent withdrawal form (copy).

Date：_______________

Signature：

Signature of the representative※：_______________（Relationship:）※

When the person's intention to withdraw consent cannot be confirmed.

Date of confirmation by physician
or person in charge of the treatment：

Signature of physician
or person in charge of the treatment：

Shonan Kamakura General Hospital Ver.2.2
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変更対比表作成年月日：2023 年 3 月 30 日
治療課題名：『自家末梢血 CD34 陽性細胞移植による下肢血管再生療法（治療）』以下に、「1-5 再生医療等を受ける者に対する説明文書及び同意文書の様式」（インバウンド用同意説明文書英語版/For Patient Reference）における修正箇所について修正・追加を下線、削除を、二重取消線として示す。

訂正箇所
フッター

p.30
17. ForInquiries
Attendinf
PhysicianVer. 2.1

Ver. 2.2

Shonan Kamakura General Hospital Ver.2.1
Date of Creation: February 24, 2023

変更理由

Shonan Kamakura General Hospital Ver.2.2 版の更新
Date of Creation: March 30, 2023

Name of Physicians：Sumi Hidaka M.D., Kunihiro Name of Physicians：Sumi Hidaka M.D., Kunihiro 医師削除にIshioka M.D., Yasuhiro Mochida M.D. Machiko Ishioka M.D., Yasuhiro Mochida M.D. Machiko よる変更
Oka M.D., Toshihiro Shimizu M.D., Naoki Oka M.D., Ayaka Mitomo M.D.
Fujiwara M.D., Ayaka Mitomo M.D.
Contact：Shonan Kamakura General Hospital
Contact：Shonan Kamakura General Hospital
Phone：0467-46-1717
Phone：0467-46-1717
以上-1-