Stem Cell Therapy to Improve Burn Wound Healing

The study will include a Phase 1 trial. A tissue repository will be collected. The recipients
in the Phases 1 of the study will be inpatients at Jackson. Their enrollment will continue
into the outpatient setting. The donors will be recruited through the University of Miami
(UM). The donors will present for 2 clinic visits, and after the bone marrow aspiration, the
study team will contact the donor by phone 2 times (Initial call 24-48 hrs. and then 30-60
days after Donation).

RECIPIENTS

Recipients will be screened upon presentation to the hospital. To establish enrollment, the
wound will be examined and measured. A complete medical history and physical exam will be
performed. Blood will be collected to test for blood bourne pathogens, including hepatitis
and HIV. A pregnancy test will be done for females. Once the patient is enrolled, MSC's will
be applied according to the dose and frequency determined by the Phase 1 trial. At various
intervals, skin biopsies, wound measurements, questionnaires and possibly bone marrow
aspirate may be performed (see below).

Study Design for Specific Phase 1:

This will represent the Phase 1 portion of the study. It will asses the safety of delivering
MSC's to burn wounds. A total of 20 patients will be recruited and divided into 4 groups.
These groups will be taken through a dose escalation method, i.e. the first group will be
started on the lowest dose. If there are no adverse reactions, the second group will receive
a higher dose. This will be repeated for the third and fourth groups with each receiving a
higher dose. If necessary, a second dose of MSC's will be given. Each administration will be
given no less than 10 days apart but no more than 6 weeks apart. Second doses will not be
given until it is evident that no significant adverse events occured from the first
administration. There will be a maximum of 2 administrations of MSC's. At the end of each
dose level, safety data will be presented to the Data Safety and Monitoring Board (DSMB) and
the Institutional Review Board (IRB). If there were no significant adverse events or concerns
from either party, the protocol will continue to the next dose level.

Rejection will be monitored with blood tests before, between and after receiving MSC's, as
well as clinical evaluation. Upon discharge from the hospital, patients will be asked to come
to clinic at 1- 4 week intervals depending on the course of the individual patient. Home
nursing care may be arranged if necessary for dressing changes. During clinic visits, the
wounds will be assessed and questionnaires done. During this time, the patients will also
have necessary evaluations and sessions with physical and occupational therapy. Once the
wound is considered healed, patients may be asked to return to clinic monthly to ensure that
the wound remains healed.

At the completion of the Phase 1 trial, all safety data will be sent to the DSMB, monitor,
IRB and FDA. If no significant safety issues arise, the study is anticipated to progress to
Phase 2 .

Blood sample and tissue repository:

During the course of the study, many samples will be taken. These include serum, blood cells,
tissue and skin cells. These samples may be taken from donors and recipients. These samples
may be able to provide insight into biomarkers which may be used to predict healing and
scarring. As such, they may be stored for further, non-clinical research in the tissue
repository. Patients would have signed away their rights to these samples.

SCHEDULE FOR RECIPIENTS (all Phase 1 patients).

Week 1:

Health and medications will be recorded. Samples of blood will be drawn for safety and
research purposes. A skin biopsy from the wound may be performed and the wound will be
evaluated/measured. Prior to treatment, 2nd degree burn subjects will be reassessed to
determine if wound healing is likely within the next week. If > 30% of the wound is closed
and significant evidence of healing is present, this subject will be excluded from further
participation in the study.

MSC's will be applied to the wound. A film dressing to hold the cells in place may be
applied. This dressing would be removed 12-48 hours post-operatively. The wound will be
dressed with the appropriate dressing for the specific type of wound. Wounds will also be
photographed.

Week 3 to 26:

Patients will return to clinic. Additional samples of blood may be obtained for research
purposes. Questionnaires will be completed with inquiries into changes in health and
medications. Wounds will be evaluated and measured, as well as photographed. Dead tissue will
be cleaned if necessary. Appropriate dressing changes will be done. If needed, MSC's will be
applied to wounds for the second time. The application will be no less than 10 days apart but
no more than 6 weeks apart. Again if cells are applied, a film dressing to hold the cells in
may be applied. This dressing can be removed in 12-48 hours.

Signs of rejection will be monitored. Blood tests will be done per investigators discretion.
Skin biopsies may also be performed. If rejection or reaction is suspected, patients will no
longer be eligible to receive any more donor cells.

After Week 26 or End of Treatment Visit:

If the wound is healed, a biopsy of the wound may be done. Samples of blood may be drawn for
research purposes. These patients will return to clinic monthly to ensure that the wound
stays closed. If the wound remains unhealed, it will be measured and photographed. Note that
patients with healed wounds may refuse biopsy. Appropriate dressing changes will be done.
Questions about health and medications will be asked.

DONORS

Approximately 10 donor will be used to harvest MSC's. Initially, potential donors will
present for a screening visit. Here, a physical exam will be done, in addition to a screening
questionnaire. Medical history will be collected. Blood samples will also be taken to be
tested for blood bourne pathogens, including hepatitis and HIV. A urine sample will be
collected as well. If a potential donor meets the screening criteria, they will return for a
second, 'donation' visit. At this visit, vital signs will be recorded and a bone marrow
aspirate will be done. The bone marrow aspirates will be done by Dr. John Byrnes, a
hematologist/oncologist who routinely performs these aspirates for the stem cell trials here
at UM. This second visit will take place within 1 week of the initial visit. A biomarker test
may be involved. The evaluation of specific biomarkers may help to determine the effect of
stem cell delivery to burn wounds. In order to provide this type of examination, removal and
analysis of nucleic acids derived from donor materials may be needed. A separate genetic
research consent will be provided to the donor.

GENETIC TESTING

The biomarker/genetic tests may be performed on materials obtained from both donors and
recipients. The samples could include bone marrow aspirate, blood and tissue. The tests will
be performed primarily to detect the expressions of levels of genes important for healing,
tissue repair and inflammation.

- Donors:

Eligibility Criteria:

- No history of malignancy

- No active coagulopathy and/or hypocoagulable state

- No history of cardio/pulmonary conditions

- Negative tests for Hepatitis A, Hepatitis B, Hepatitis C, RPR, HIV 1 / 2, HTLV I/II,
Chagas Disease, NAT for HCV, HIV and WNV.

- Hemoglobin ≥ 13.0 g/dL

- Platelet count 140,000 to 440,000/ul

- WBC 3.0 to 11.0 K/ul

- BNP ≤ 100 pg /mL

- No anomalies on the CBC and differential suggestive of a hematopoietic disorder

- Creatinine ≤ 1.5 mg/dL

- ALT ≤ 112 IU/L

- AST ≤ 100 IU/L

- Bilirubin < 1.5 mg/dL

- No diabetes

- Systolic blood pressure ≤ 170

- Diastolic blood pressure ≤ 90

- No history of autoimmune disorders

Recipients:

Inclusion Criteria:

1. Male or female subjects 18 years of age or older with Superficial, Intermediate or
Deep 2nd Degree Burn Wounds

2. Injury within the prior 7 days

3. Subjects must understand and give written informed consent.

4. Subjects must agree to have biopsies performed as per protocol

5. Subjects must be accessible for weekly wound treatment and assessment visits

6. Males and females must agree to use an acceptable method of contraception. Exceptions
will be females of non-childbearing age and monogamous males who are partners of
females of non-childbearing age. Acceptable methods of birth control include; history
of sterilization, birth control pills, depoprogesterone injections, a barrier
contraceptive such as a condom with or without spermicide cream or gel, diaphragms or
cervical cap with or without spermicide cream or gel, or an intrauterine device (IUD).

7. Maximum wound size limited to:

- Single wound: ≤ 5% body surface area (BSA)

- Multiple wounds treated in a defined anatomical region with ≤ 20% cumulative BSA.

8. Diabetic subjects: HbA1c ≤ 8%

Exclusion Criteria:

1. Solely 1st degree or solely 3rd degree burns

2. Subjects with superficial 2nd degree burn who are expected to heal within 2 weeks post
standard therapy

3. Evidence of active infection at the wound site

4. Evidence of significant wound healing prior to treatment

5. Wound located in the area of fingers, toes, face, or perineum

6. Wound where 75% or more extends across joints

7. Electrical or chemical burns

8. Have any requirement for the use of systemic steroids or immunosuppressive

9. Subjects Allergic to human albumin, streptomycin, or penicillin

10. Be a pregnant female or nursing mother

11. Subjects who are known or found to be HIV positive

12. Current history of alcohol or substance abuse or history of alcohol or substance abuse
requiring treatment within the past 12 months

13. Patients with severe medical conditions

1. Malignancy (other than non melanoma skin cancer) not in remission or in remission
less than 5 years

2. Life expectancy less than two years

3. Severe cardiopulmonary disease restricting ambulation to the clinical facility

14. WBC <3 or > 10 x10⁹/L, Hgb < 9g/dL, platelets count 100x10⁹/L or less, serum
creatinine > 1.5 times the upper normal limit, AST or ALT > 2.5 times the upper normal
limit.

15. Subjects with abnormal bilirubin levels.

16. Subjects with abnormal PT/INR laboratory values while not on chronic anticoagulant
treatment which can be held for minor surgical procedures

17. Those with a known history of coagulopathy

18. Subjects who are potential recipients of tissue or organ transplantation

19. Subjects with circulating Hepatitis B antigen and/or who are seropositive for
Hepatitis C antibody

20. History of poor compliance, unreliability