A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation

This is a phase I single center open label trial study that will enroll sixteen patients
requiring semi-elective lower extremity major amputation within a 30 day period for
non-infectious complications related to critical limb ischemia (CLI). After enrollment
patients will be randomized to amputation at 3,7,14, or 21 days after MSC administration. The
investigational treatment uses allogeneic bone marrow derived mesenchymal stem cells at the
point of care. Allogeneic MSCs will be injected in the thigh muscles and the gastrocnemius
muscle (for below knee amputation only) of sixteen patients undergoing major amputation.
Through a review of treatment related adverse events over 6 months we will test the
hypothesis that allogeneic MSCs do not result in significant cardiovascular, respiratory, or
infectious treatment related adverse events. Through an exploratory investigation we will
assess the efficacy of MSCs in promoting freedom from gangrene, revision of amputation, and
death after major amputation.

Inclusion Criteria:

1. Be ≥ 40 and ≤90 years of age.

2. Patients requiring lower extremity major amputation, as determined by an independent
vascular specialist.

3. If ulceration or gangrene present, it is distal to malleoli (to allow adequate length
of ATM area of approximately 3cm^2 x 2 cm^2)

4. Amputation can safely be performed up to 30 days after screening, as determined by an
independent vascular or orthopedic surgeon.

5. Females of childbearing potential must be willing to use one form of birth control for
the duration of the study. Female participants must undergo a blood or urine pregnancy
test at screening.

Exclusion Criteria:

1. Patients who are pregnant, planning to become pregnant in the next 12 months, or
lactating.

2. Significant hepatic dysfunction (ALT or AST greater than 2 times normal).

3. CHF hospitalization within the last 1 month prior to enrollment.*

4. Acute coronary syndrome in the last 1 month prior to enrollment.*

5. HIV positive, or active, untreated HCV.

6. History of cancer within the last 5 years, except basal cell skin carcinoma

7. Any bleeding diathesis defined as an INR ≥ 2.0 (off anticoagulation therapy) or
history of platelet count less than 70,000 or hemophilia.

8. Inability to provide written informed consent due to cognitive or language barriers
(interpreter permitted).

9. Concurrent enrollment in another clinical investigative trial.

10. Any condition requiring immunosuppressant medications (e.g., for treatment of organ
transplants, psoriasis, Crohn's disease, alopecia areata).

11. Presence of any clinical condition that in the opinion of the PI or the sponsor makes
the patient not suitable to participate in the trial.

- As defined by the standard definitions of CHF and ACS by the American Heart
Association.