, a dual intramuscular and intra-arterial autologous BM-MNC implantation strategy was employed in nine patients for whom limb amputation was recommended. Following the procedure,

there was no significant improvement in ABI. Three (33.3%) underwent major amputations. The remaining six patients demonstrated an improvement in rest pain. Complete wound healing was achieved within 3 months in all patients who had ulcers.27 In a study comparing exclusive IM (n = 12) versus combined IM plus IA (n = 15) delivery of autologous BMC, there were no adverse reactions related to injection of the cells.28 Two patients in the IA plus IM group required limb amputation because of ongoing critical ischemia Inhibitors,research,lifescience,medical versus seven patients in the IM group (P = 0.17). The remaining patients had a significant and sustained (>12 months) improvement Inhibitors,research,lifescience,medical in pain-free walking, mean ABI, and pain scores within 6 weeks follow-up.28 Similar findings were seen in the TAM-PAD study.29 Summary: The Cochrane database included only two small studies (57 patients); these showed

that the treatment groups experienced a greater reduction in rest pain (P < 0.001) and an increase in ABI with Inhibitors,research,lifescience,medical a statistically significant increase in pain-free walking distance (mean increase 306.4 m versus 78.6 m, P = 0.007) compared to the control groups. However, a smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007).30 The authors stressed the need for further randomized controlled clinical trials to interpret the impact of cell therapy on clinical outcomes. In a meta-analysis

of autologous cell therapy to treat patients with critical limb ischemia, researchers identified 37 trials (controlled and noncontrolled, randomized Inhibitors,research,lifescience,medical and nonrandomized trials) using autologous bone marrow or granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood cells.31 Autologous cell therapy was effective in improving Inhibitors,research,lifescience,medical surrogate indexes of ischemia, subjective symptoms, and hard endpoints (ulcer healing and amputation). On the contrary, G-CSF monotherapy was these not associated with significant improvement in the same endpoints. Patients with thromboangiitis obliterans showed some larger benefits than patients with atherosclerotic CLI. The intramuscular route of administration and the use of bone marrow cells seemed somehow more effective than intra-arterial administration and the use of mobilized peripheral blood cells. This meta-analysis indicates that intramuscular autologous bone marrow cell therapy is a feasible, relatively safe, and potentially effective therapeutic strategy for PAD patients who are not candidates for traditional revascularization. Cardiovascular Molecular and Cell Therapy Program at click here Methodist The Cardiovascular Molecular and Cell Therapy Program at The Methodist Hospital is a multidisciplinary program that promotes clinical trials in cardiovascular disease.