Journal Article

Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes

Shangzhu Li, Renchi Yang, Zhijian Xiao, Zhong Chao Han, Pingping Huang, Mingzhe Han

2005

Overview

Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes Pingping Huang , MD 1 2 , Shangzhu Li , MSPH 1 , Mingzhe Han , PHD 1 , Zhijian Xiao , MD 1 , Renchi Yang , MD 1 and Zhong Chao Han , PHD, MD 1 2 1 National Research Center for Stem Cell Engineering and Technology, State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union of Medical College, Tianjin, China 2 TEDA Center of Life Science & Technology, Tianjin, China Address correspondence and reprint requests to Dr. Zhong Chao Han, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union of Medical College, 288 Nanjing Rd., Tianjin, 300020, China. E-mail: tihzchan{at}public.tpt.tj.cn Abstract 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 CLI were 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 μg/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 ± 0.11 to 0.57 ± 0.14 perfusion units ( P < 0.001). Mean ankle-brachial pressure index increased from 0.50 ± 0.21 to 0.63 ± 0.25 ( P < 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 = 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 = 0.007, transplant vs. control group). Angiographic scores were significantly improved in the transplant group when compared with the control group ( P = 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. ABI, ankle-brachial pressure index CLI, critical limb ischemia EPC, endothelial progenitor cell G-CSF, granulocyte colony–stimulating factor PAD, peripheral arterial disease PBMNC, peripheral blood mononuclear cell Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted June 13, 2005. Received February 3, 2005. DIABETES CARE

• Publisher: American Diabetes Association
• Subject: Aged / amputation / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Applied cell therapy and gene therapy / Associated diseases and complications / Biological and medical sciences / Care and treatment / cell transplantation / Cells / colony-stimulating factors / Debridement / Diabetes / Diabetes. Impaired glucose tolerance / Diabetic angiopathies / Diabetic Angiopathies - therapy / Diabetic Foot - epidemiology / Effectiveness studies / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Extremities - blood supply / Female / Foot Ulcer - epidemiology / glycemic control / Granulocyte colony-stimulating factor / Granulocyte Colony-Stimulating Factor - therapeutic use / Hematopoietic Stem Cell Mobilization - methods / Humans / intramuscular injection / Ischemia / Ischemia - therapy / Leukocytes / limbs (animal) / Male / Medical sciences / Medical treatment / Middle Aged / Necrosis / Neutrophils - transplantation / Physiological aspects / recombinant fusion proteins / Recombinant Proteins / Safety / subcutaneous injection / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transplantation / Transplantation, Autologous / Transplants & implants / Treatment Outcome