自体外周血单个核细胞移植治疗严重肢体缺血30例:3年安全性随访

Autologous peripheral blood mononuclear cells transplantation in treatment of 30 cases of critical limb ischemia:3-year safety follow-up

背景:应用干细胞治疗成为血管性疾病治疗研究的热点。目前尚无相关诊疗标准,也未发现远期安全性报道。目的:评估血液干细胞移植标准化方案治疗严重肢体缺血的安全性、有效性和可行性。方法:将60例严重肢体缺血患者(糖尿病足30例,动脉硬化闭塞症22例,血栓闭塞性脉管炎8例),随机分为移植组和对照组。移植组患者接受了连续5d的重组人粒细胞集落刺激因子(600μg/d)的皮下注射,以此来动员干/祖细胞,然后采集外周血单个核细胞,多点肌肉注射。所有的患者接受3个月的疗效随访,移植组患者接受3年以上的安全性随访。结果与结论:移植组患者的主要临床症状体征包括下肢疼痛和溃疡明显改善,激光多普勒血流仪的测定结果显示他们的下肢动脉血流量从(0.42±0.13)灌注单位增加到(0.59±0.12)灌注单位(P<0.001),平均踝肱指数在0.47±0.22的基础上增加到0.59±0.27(P<0.001)。移植组患者中有70.0%(28/40)溃疡完全治愈,而对照组患者中只有26.8%(11/41)的溃疡被治愈(P=0.012);相比对照组,移植组患者的血管造影评分显著改善(P=0.002)。移植组1例患者进行了截肢,而对照组5例患者接受下肢截肢(P=0.005)。移植组3年的安全性随访未发现移植相关不良反应。结果表明血液干细胞移植标准化方案治疗严重肢体缺血是简单、安全、有效的。

BACKGROUND：Stem cell therapy for vascular diseases has been a hot research point.At present,no reports have addressed diagnostic criteria or long-term safety.OBJECTIVE：To assess safety,efficacy and feasibility of the application of autologous transplantation of peripheral blood stem cells（PBSC） in the treatment of critical limb ischemia（CLI）.METHODS：A total of 60 patients with CLI（30 cases of diabetic foot,22 cases of atherosclerosis obliterans and 8 cases of thromboangiitis obliterans） were enrolled and randomized to the transplant group and control group.In the transplant group,the patients received subcutaneous injection of recombinant human granulocyte colony-stimulating factor（G-CSF）（600 μg/d） for 5 days to mobilize stem/progenitor cells,and their peripheral blood mononuclear cells were collected and transplanted by multiple intramuscular injections into ischemic limbs.All patients were followed up after at least 3 months,but those in the transplant group were at least 3 years.RESULTS AND CONCLUSION：The main manifestations,including lower limb pain and ulcers,were significantly improved in patients of the transplant group.The results of laser Doppler flowmetry showed that blood perfusion of lower limbs increased from（0.42±0.13） to（0.59±0.12） perfusion units（P 0.001）.Mean ankle-brachial pressure index was increased from（0.47±0.22） to（0.59±0.27）（P 0.001）.A total of 28 of 40 limb ulcers（70.0%） of transplanted patients were completely healed after cell transplantation,whereas only 26.8% of limb ulcers（11 of 41） were healed in the control patients（P=0.012）.Angiographic scores were significantly improved in the transplant group compared with the control group（P = 0.002）.One patient received a lower limb amputation in the transplanted patients.In control group,five control patients received a lower limb amputation（P = 0.005）.No adverse effects specifically related to cell transplantation were observed in the transplant group at least 3 years after treatment.These results indicate that blood stem cell transplantation standard scheme for CLI is simple,safe and effective.