Abstract 8381: Safety and Effect of Adipose Tissue Derived Stem Cell Implantation in Patients with Critical Limb Ischemia

Abstract

Adipose tissue-derived mesenchymal stem cells (ADSCs) are potent and effective for inducing regeneration of damaged tissue. Treatment of critical limb ischemia (CLI) is occasionally difficult through bypass operation or percutaneous vascular intervention. ADSC transplantation shows proangiogenic action in animal hindlimb ischemia models. We performed multiple intramuscular ADSC injections in CLI patients to treat diabetic foot and thromboangiitis obliterans (TAO) and assessed its safety and efficacy. The study included 15 CLI patients (15 men, median age: 52 years, range: 24-73 years) with ischemic resting pain in one limb with/without nonhealing ulcers and necrotic foot (Rutherford class II-4: n = 3, III-5: n = 9, III-6: n = 3) who did not undergo nonsurgical or surgical revascularization. ADSCs were isolated from adipose tissue of TAO patients (B-ADSCs), diabetes patients (D-ADSCs), and healthy donors (control ADSCs) by using 0.075% collagenase digestion. In a colony forming unit (CFU) assay using stromal vascular fraction, B-ADSCs and D-ADSCs yielded lesser colonies than normal ADSCs. However, culture-expanded B-ADSCs showed normal proliferation ability compared to control ADSCs. Adipogenic and osteogenic differentiation potential did not differ between B-ADSCs and control ADSCs. Culture-expanded D-ADSCs showed lower proliferation ability and osteogenic differentiation and higher adipogenic differentiation than control ADSCs. Multiple intramuscular ADSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up. All amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography (DSA) before and 6 months after ADSC implantation showed formation of numerous vascular collateral networks across affected arteries. Multiple intramuscular ADSC injections may be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities