自体骨髓干细胞移植治疗下肢缺血性疾病60例

Autologous bone marrow stem cell transplantation in treatment of 60 cases of lower limb ischemia

背景：动物实验已经证实，来源于骨髓或外周血干细胞能够在血管损伤部位分化形成新生血管，进而改善肢体血液供应。目的：观察自体骨髓干细胞移植治疗慢性下肢缺血的临床疗效。设计、时间及地点：自身对照加非随机对照的双盲试验，于2004-09／2007-09在山东大学附属省立医院血管外科及科研中心完成。对象：受试对象为下肢血管缺血性病变失去外科手术或介入治疗适应症，并愿意接受自体干细胞移植的患者60例，男36例，女24例，年龄33—83岁，平均65岁。方法：实验采用干细胞分离液，利用梯度密度法分离患者自体骨髓干细胞，制备干细胞悬液。根据缺血范围选取缺血肢体肌肉多点穿刺注射。主要观察指标：以治疗后6个月患者下肢疼痛症状、行走能力、皮肤溃疡、踝肱指数、足坏疽评分的变化来评价临床疗效。结果：治疗后6个月，患肢疼痛、麻木感和冷感觉改善率为78．33％，47例患者静息痛消失或明显减轻，5例患者跛行距离由不足50m提高到大于100m，10例伴有溃疡的患者，溃疡愈合或面积逐渐减小。11例踝肱指数增加大于0．1，4例足趾坏疽患者中1例症状明显缓解，静息痛消失，行坏疽足趾切除，愈合良好；2例疼痛消失，睡眠改善，坏疽组织有脱落迹象：1例于膝下截肢。结论：自体骨髓干细胞移植对肢体疼痛、冷感、麻木疗效确切，对创面愈合有促进作用。

BACKGROUND： Bone marrow derived or peripheral blood derived stem cells have been proved though animal model to participate in the vasculogenesis of infarcted area and thus to improve limb blood supply. OBJECTIVE： To evaluate the efficacy of autologous transplantation of bone marrow stem cells （BMSCs） for treating chronic ischemia of the lower limbs. DESIGN, TIME AND SETTING： The self-consistency validation plus non-randomized control, double-blind study was performed at the Department of Vascular Surgery and Central Laboratory in Shandong Provincial Hospital Affiliated to Shandong University from September 2004 to September 2007. PARTICIPANTS： Totally 60 aged patients with chronic ischemia of the lower limb, who had no chance of surgery or interventional treatment and were willing to receive autologous BMSC transplantation, were enrolled, including 36 males and 24 females, with a mean age of 65 years ranged from 33 to 83 years. METHODS： Autologous BMSCs were isolated by density gradient centdfugation with stem cell extract liquid to prepare stem cell suspension, and were intramuscularly injected into the suffered limbs. The range and position of puncture depend on the area of lymphedema. MAIN OUTCOME MEASURES： The clinical outcomes of patients were assessed by pain symptom, walking ability, skin ulcer, anlde-brachial index and foot gangrene score of the lower limbs 6 months following treatment. RESULTS： Six months after treatment, the symptoms of pain, paresis, and coldness were alleviated, resulting in an improvement rate of 78.33%. The rest pain was relieved completely or partially in 47 patients, the distance of intermittent claudication was increased from less than 50 m to more than 100 m in 5 patients, and the ulcers of 10 patients healed up or reduced in size. Moreover, the ankle braehial index in 11 patients increased by more than 0.1. As for the four patients with toes gangrene, one got rid of the rest pain and other symptoms, and had a good wound healing after resecting the gangrenous toes; two got rid of the pain, sleep was improved and the gangrenous tissue began to exfoliate; another one was subjected to a below-knee amputation. CONCLUSION： Autologous BMSC transplantation has definite effects on pain, coldness and paresis of patients, and can promote wound healing.