OBJECTIVE -To assess the application of autologous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMNCs) in the treatment of critical limb ischemia (CLI) of diabetic patients and to evaluate the safety, efficacy, and feasibility of this novel therapeutic approach. RESEARCH DESIGN AND METHODS -Twenty-eight diabetic patients with CLIwere enrolled and randomized to either the transplant group or the control group. In the transplant group, the patients received subcutaneous injections of recombinant human G-CSF (600 g/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs. All of the patients were followed up after at least 3 months.RESULTS -At the end of the 3-month follow-up, the main manifestations, including lower limb pain and ulcers, were significantly improved in the patients of the transplant group. Their laser Doppler blood perfusion of lower limbs increased from 0.44 Ϯ 0.11 to 0.57 Ϯ 0.14 perfusion units (P Ͻ 0.001). Mean ankle-brachial pressure index increased from 0.50 Ϯ 0.21 to 0.63 Ϯ 0.25 (P Ͻ 0.001). A total of 14 of 18 limb ulcers (77.8%) of transplanted patients were completely healed after cell transplantation, whereas only 38.9% of limb ulcers (7 of 18) were healed in the control patients (P ϭ 0.016 vs. the transplant group). No adverse effects specifically due to cell transplantation were observed, and no lower limb amputation occurred in the transplanted patients. In contrast, five control patients had to receive a lower limb amputation (P ϭ 0.007, transplant vs. control group). Angiographic scores were significantly improved in the transplant group when compared with the control group (P ϭ 0.003).CONCLUSIONS -These results provide pilot evidence indicating that the autologous transplantation of G-CSF-mobilized PBMNCs represents a simple, safe, effective, and novel therapeutic approach for diabetic CLI. Diabetes Care 28:2155-2160, 2005D iabetes is a common chronic disease with significant morbidity and mortality. One devastating complication of diabetes is peripheral arterial disease (PAD) including critical limb ischemia (CLI), which may result in limb loss. There is no available permanent cure for diabetic CLI at present (1,2).Several investigations have indicated that in patients with diabetes, the circulating endothelial progenitor cells (EPCs) exhibit impaired proliferation, adhesion, and incorporation into vascular structures. The adverse metabolic stress factors are associated with reduced number and dysfunction of EPCs (3,4). In response to tissue injury and remodeling, neovascularization usually occurs via the proliferation and migration of endothelial cells from preexisting vasculature (5). However, the EPCs resident within bone marrow and peripheral blood (6 -8) can also contribute to injury-induced and pathology-induced neovascularization. In animal models of diabetes, transplantation of bone marrow-or blood-derived EPC...

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These results suggest that decreased number and function of Treg cells might be one of mechanisms that cause immune regulation dysfunction in ITP.