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 twenty-six (26) 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 scheduled for amputation 7 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 gastrocnemius muscle and anterior tibialis muscle of twenty-six (26) 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

• Be ≥ 40 and ≤90 years of age.
• Patients requiring lower extremity major amputation, as determined by an independent vascular specialist.
• If ulceration or gangrene present, it is distal to malleoli (to allow adequate length of ATM area of approximately 3cm x 10cm x 3 cm)
• Amputation can safely be performed up to 30 days after screening, as determined by an independent vascular or orthopedic surgeon.
• 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

• Patients who are pregnant, planning to become pregnant in the next 12 months, or lactating.
• CHF hospitalization within the last 1 month prior to enrollment.*
• Acute coronary syndrome in the last 1 month prior to enrollment.*
• HIV positive, or active, untreated HCV as determined by review of medical records.
• History of cancer within the last 5 years, except basal cell skin carcinoma
• Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).
• Concurrent enrollment in another clinical investigative trial that may alter the outcomes of enrollment in this trial.
• Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
• 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.