【作者】 李学锋；

【导师】 沈振亚；

【作者基本信息】 苏州大学 ， 外科学， 2011， 博士

【摘要】 目的:观察骨髓刺激后骨髓源干细胞移植治疗肢体缺血性疾病的疗效;探讨骨髓刺激后自体骨髓源干细胞移植治疗肢体缺血性疾病的机制。研究方法:本研究分为三部分。第一部分为骨髓刺激后骨髓源干细胞移植治疗肢体缺血性疾病的基础研究,在动物模型上比较骨髓刺激与非刺激骨髓源干细胞移植后对动物缺血肢体血流重建的影响,并探讨其作用机制,为临床研究提供理论基础;第二部分和第三部分分别为骨髓刺激后骨髓源干细胞移植治疗下肢动脉硬化闭塞症和血栓闭塞性脉管炎的临床研究,从临床角度观察骨髓刺激后骨髓源干细胞移植对缺血肢体血流重建的影响。结果:基础研究:1、骨髓刺激组迁移细胞数目明显多于骨髓未刺激组;骨髓刺激组黏附细胞数目明显多于骨髓未刺激组。2、行骨髓源内皮祖细胞移植的骨髓刺激组侧支血管数目、CD31阳性细胞数目、肢体血流百分比的增加和VEGFmRNA表达水平明显多于骨髓未刺激组。临床研究:1、在抽取骨髓血量接近的情况下,骨髓刺激组获取的细胞数明显多于骨髓未刺激组。2、骨髓刺激组移植细胞中CD34+细胞所占比例明显高于骨髓未刺激组。3、骨髓刺激组较骨髓未刺激组主观症状及部分客观指标有明显改善。结论:1、骨髓刺激后骨髓源干细胞移植对下肢动脉硬化闭塞症和血栓闭塞性脉管炎患者肢体缺血的改善优于未刺激的骨髓源干细胞移植。2、骨髓刺激提高骨髓源干细胞移植改善肢体缺血疗效的机制可能是骨髓源内皮祖细胞数量的增加和功能的改善。3、骨髓刺激后骨髓源干细胞移植是传统骨髓干细胞移植治疗肢体缺血性疾病方案的补充和优化。更多还原

【Abstract】 Objectives:We observed the effectiveness of bone marrow stem cells transplantation to treat the limb ischemic diseases after the bone marrow stimulation and researched the mechanism of bone marrow stem cells transplantation to treat the limb ischemic diseases after the bone marrow stimulation.Methods:Three parts were consisted of this research. The part 1 was focus on the experimental research of bone marrow stem cells transplantation to treat the limb ischemic disease after the bone marrow stimulation. In this part, the effectiveness of bone marrow stem cells transplantation on the animal models with the bone marrow stimulation were compared with the animal models without the bone marrow stimulation. The results of this part provided the theoretic basis for the clinical research. The part 2 and the part 3 were the clinical researches of bone marrow stem cells transplantation for the treatment of Arteriosclerosis Obliterans(ASO) and Thromboangiitis Obliterans(TAO) after the bone marrow stimulation respectively.Results:Experimental research:1 The number of migrating and adhering cells in the bone marrow stimulating group were significantly increased in comparison with the non-stimulating group.2 The number of collateral branches of the vessel, CD31 positive cells and the expressing level of VEGFmRNA in the bone marrow stimulating group were significantly increased in comparison with the non-stimulating group.Clinical research: 1 The number of Bone Marrow-Mononuclear Cells (BM-MNCs) in the bone marrow stimulating group was significantly higher than it in the non-stimulating group under obtaining the similar volume of the bone marrow blood.2 The percent of CD34 positive cells in the bone marrow stimulating group was significantly higher than it in the non-stimulating group3 The symptoms and the part of objective indexs in the bone marrow stimulating group were significantly improved in comparison with the non-stimulating group.Conclusions:1 The capabilities of revascularization after the bone marrow stem cells transplantation in the bone marrow stimulating group were obviously superior to the capabilities of revascularization in the non-stimulating group for the treatment of ASO and TAO.2 The mechanisms of bone marrow stem cells transplantation after the bone marrow stimulation for the treatment of the lower limb ischemia may be the increasing of endothelial progenitor cells’(EPCs)number and the improvement of EPCs’functions.3、Bone marrow stem cells transplantation after the bone marrow stimulation is a supplement and optimization of the traditional bone marrow stem cells transplantation for the treatment of the limb ischemic diseases.更多还原