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...

Mesenchymal stem cells (MSCs) reside in almost all of the body tissues, where they undergo self-renewal and multi-lineage differentiation. MSCs derived from different tissues share many similarities but also show some differences in term of biological properties. We aim to search for significant differences among various sources of MSCs and to explore their implications in physiopathology and clinical translation. We compared the phenotype and biological properties among different MSCs isolated from human term placental chorionic villi (CV), umbilical cord (UC), adult bone marrow (BM) and adipose (AD). We found that CD106 (VCAM-1) was expressed highest on the CV-MSCs, moderately on BM-MSCs, lightly on UC-MSCs and absent on AD-MSCs. CV-MSCs also showed unique immune-associated gene expression and immunomodulation. We thus separated CD106+cells and CD106−cells from CV-MSCs and compared their biological activities. Both two subpopulations were capable of osteogenic and adipogenic differentiation while CD106+CV-MSCs were more effective to modulate T helper subsets but possessed decreased colony formation capacity. In addition, CD106+CV-MSCs expressed more cytokines than CD106−CV-MSCs. These data demonstrate that CD106 identifies a subpopulation of CV-MSCs with unique immunoregulatory activity and reveal a previously unrecognized mechanism underlying immunomodulation of MSCs.