自体外周血及骨髓干细胞移植治疗糖尿病下肢动脉闭塞：随机对照

Combined transplantation of autologous peripheral blood and bone marrow stem cells for the treatment of diabetic lower limb ischaemia: Randomized controlled trial

目的：观察自体外周血干细胞和骨髓干细胞联合移植治疗糖尿病下肢闭塞症的临床疗效。方法：选择2003—09／2007-01河南省人民医院二内内分泌科194例糖尿病下肢闭塞症患者，随机分为对照组（n=95）和干细胞移植组（n=99），2组均接受内科综合治疗，在此基础上对干细胞移植组进行干细胞移植，95例患者双侧肢体行自体干细胞移植，3例仅缺血较重的一侧肢体行自体干细胞移植，1例因一侧肢体截肢，另一侧行肢体干细胞移植，干细胞移植的肢体为194条，患者对治疗知情同意，并经医院伦理委员会批准。对干细胞移植组患者进行外周血干细胞动员，每天给予人重组粒细胞集落刺激因子450～600u，皮下注射，第5天局部麻醉下从髂骨处抽取自体骨髓血200mL，在实验室将骨髓沉淀、离心，分离等处理后制备40mL干细胞悬浊液备用。第6天应用COBE6．1血细胞分离机单采单个核细胞，总量60-120mL。将两种干细胞悬液按3cm×3cm距离进行缺血肢体移植术，移植后2周观察症状、体征改变。结果：①干细胞移植组疼痛症状明显缓解、好转、无效的肢体分别为94个、96个、4个，对照组分别7个、156个、27个，2组间显效率及无效率差异显著（P〈0．01）。②干细胞移植组冷感明显缓解、好转、无效的肢体分别为126个、63个、5个，对照组分别为6个、158个、26个，2组间显效率及无效率差异显著（P〈0．01）。③干细胞移植组间歇性跛行明显缓解、好转、无效的肢体分别为138个、47个、9个，对照组分别为13个、152个、25个，2组间显效率及无效率差异显著（P〈0．01）。所有患者未出现并发症和不良反应。结论：自体外周血干细胞移植治疗糖尿病足是一种简便、安全、有效的治疗方法。

AIM： To observe the clinical efficacy of autologous peripheral blood stem cells （PBSC） and autologous bone marrow stem cells （BSC） combined transplantation in the treatment of diabetic lower limb ischaemia. METHODS： From September 2003 to January 2007, 194 patients with diabetic lower limb ischaemia were selected from the Second Department of Endocrinology, Henan Provincial People＇s Hospital and randomly divided into control group （n=95）, and treatment group （n=99）. Both two groups were treated with the same medical measures. The treatment group underwent stem cell transplantations, of which, 95 patients received bilateral transplantation, and 4 cases received unilateral limb transplantation including 3 due to severe ischemia, and 1 due to unilateral amputation. The informed consent was obtained from the patients, and the treatment was admitted by the Hospital Ethics Committee. The treatment group received recombinant human granulocyte colony-stimulating factor （450-600） u/d by hypodermic injection to mobilize stem cells. On the 5^th day, 200 mL bone marrow blood was harvested from iliac bone under anesthesia, and 40 mL stem cell suspension was prepared after bone marrow sedimentation, centrifugalization and isolation. On the 6th day, 60-120 mL mononuclear cells were collected by COBE 6.1 spectra version. The PBSC and BSC were injected into the ischemic lower limbs and foot for 3 cm × 3 cm distance. The symptoms and signs changes were observed in 2 weeks after transplantation. RESULTS： ①After transplantation for 2 weeks, the pain was significantly relieved, improved or ineffective in 94, 96 and 4 limbs of treatment group, respectively and 7, 156 and 27 limbs of control group, respectively. The efficacy and inefficacy were significantly different （P 〈 0.01）. ②The cold feelings were significantly relieved, improved or ineffective in 126, 63 and 5 limbs of treatment group, respectively and 6, 158 and 26 limbs of control group, respectively. The efficacy and inefficacy were significantly different （P 〈 0.01）. ③The intermittent claudication was significantly relieved, improved or ineffective in 138, 47 and 9 limbs of treatment group, respectively and 13, 152 and 25 limbs of control group, respectively. There were significant differences in the efficacy and inefficacy （P 〈 0.01）. No related complications or adverse effects were observed in all patients. CONCLUSION： Autologous PBSC and BSC transplantation is a safe and effective method for diabetic foot.