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Non-Reconstructable Peripheral Vascular Disease of the Lower Extremity in Ten Patients Treated With Adipose-derived Stromal Vascular Fraction Cells:  SVF cell therapy for end-stage disease
Submitted by: Michael Carstens, M.D., Diego Correa, M.D., Ph.D., Arturo Gomez, M.D., Ronald Cortés, M.D., Elizabeth Turner, M.D., Cecilia Pérez, M.D., Marlon Ocon, M.D.

BACKGROUND: Chronic limb ischemia (CLI) due to arterial insufficiency is caused by arteriosclerosis (AS), 70%, and diabetes mellitus (DM), 30%. [1, 2]   Options for these patients are often limited; 30% have non-reconstructable diease; [3, 4] thus, 9% of patients with AS and 40% of patients with DM will progress onward to tissue necrosis and/or gangrene. [5]

SVF cells produce multiple growth factors, such as VGEF that act via paracrine mechanisms to stimulate angiogenesis. [6, 7, 8, 9, 10, 11] Recent reports by Lee [12] and Casteilla, [13 using adipose-derived stem cells for CLI document improvement in walking time, ulcer healing, transcutaneous PO2 and angiography evidence of neovascularization.

OBJECTIVES: We present a clinical series of 10 patients with end-stage CLI, secondary to arteriosclerosis and/or diabetes presenting with 1/2 block claudication, rest pain and/or non-healing wounds treated with adipose-derived SVF cells administered as intramuscular and peri-lesional injection.

METHODS: 10 patients were treated, 9 females and 1 male, ranging in age from 57 to 85 years of age. 6 ulcers were present, 5 in diabetics and 1 due to AS; the wounds ranged in size from 3 cm diameter to 8 x 6 cm. SVF was obtained by liposuction, followed by collagenase digestion, centrifugation, and resuspension. The injections placed intramuscular in parallel with the arterial axis and subcutaneously beneath the ulcers. Clinical progress, in terms of pain-free ambulation and wound healing, was documented by photography, ankle/brachial (AB) ratio, and angiography.

RESULTS: All patients achieved pain relief. Ankle-brachial index improved on average 207%. Of the 6 wounds, 5 healed spontaneously; one (the largest) successfully supported a skin graft. Arteriography in seven patients demonstrated neovascularization in the distal extremity with proliferation of vessels in the posterior compartment.

CONCLUSIONS: Therapy for end-stage chronic limb ischemia using adipose-derived SVF cells was subjectively and objectively effective in these patients. The series highlights the utility of cell therapy for patients with end-stage disease as an alternative to palliation or amputation. The angiogenic properties of SVF cells may reasonably be extended to improve the biologic function of ischemic tissues at other anatomic sites.


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