Safety Study of Using Stem Cells to Stimulate Development of New Blood Vessels in Peripheral Vascular Disease

Phase I Study of Stem Cell Mediated Angiogenesis for Limb Threatening Ischemia

The purpose of this study is to determine if bone marrow derived adult stem cells are safe and effective in inducing development of new blood vessels (angiogenesis) in the legs of patients with severe peripheral vascular disease.

Presently there are no effective medical therapies to enhance blood flow in the legs of patients with peripheral vascular disease. For patients with limb threatening ischemia the only option for relief of rest pain or gangrene is amputation.

There is evidence in animal and clinical studies that adult stem cells in the bone marrow, called endothelial progenitor cells, participate in the development of new blood vessels, a process called angiogenesis. In this investigation, patients with limb threatening ischemia will have their bone marrow harvested and the stem cells will then be removed and injected directly into the muscle of the diseased leg. The procedure will require about 4 hours and the subjects will be admitted to the Indiana University Medical Center overnight. The follow-up period is 12 weeks and the analysis will consist of examinations at 1, 2, 4, 6, 8, and 12 weeks. Adverse and serious adverse events will be recorded during this time period. Diagnostic studies will be obtained to measure blood flow in the treated leg during the follow up period and include transcutaneous (skin) oxygen measurements, pressure recordings in the leg, arteriography, magnetic resonance imaging, and wound healing.

Inclusion Criteria:

• Severe peripheral vascular disease not amenable to bypass or angioplasty
• Age >21 years old
• Normal renal function (creatinine < 1.6)

Exclusion Criteria:

• Congestive heart failure (ejection fraction [EF]<30%)
• History of cancer or myeloproliferative disorders
• Proliferative retinopathy
• Pregnancy
• Cognitively disabled