双血管生成和神经营养骨髓内皮祖细胞对糖尿病神经病变的影响百替生物.pptVIP

Dual Angiogenic and Neurotrophic Effects of Bone Marrow–Derived Endothelial Progenitor Cells on Diabetic Neuropathy Jeong, Mee-Ohk Kim, et al. Circulation Lisa 2014.4.24 糖尿病慢性并发症的分布 脑血管病变 肺部感染 胃肠病变 胆囊病变 糖尿病肾病 动脉硬化 神经病变 糖尿病足 膀胱病变 糖尿病眼病 Charcot关节 心脏病变 糖尿病是以胰岛素分泌不足和胰岛素作用减低或胰岛素抵抗导致碳 水化合物、脂肪及蛋白质代谢异常，以高血糖为特征的代谢性疾病。 Introduction Introduction 糖尿病神经病变是糖尿病最常见的慢性并发症之一，病变可累及中枢神经及周围神经，后者尤为常见。其中远端感觉神经病变是最常见的病变，占所有糖尿病神经病变的50%以上。 糖尿病神经病变可能发病机制： （1）遗传因素 （2）氧化应激： （3）多元醇通路过度活跃 （4）必需脂肪酸代谢异常 （5）血管病变（血液流变性异常，血管结构障碍，血管活性因子改变） （6）神经生成营养因子缺乏：包括神经生长因子（NGF）、IGF-1等 内皮祖细胞(endothelial progenitor cells,EPCs)是血管内皮细胞的前体细胞, 在生理或病理因素刺激下,可从骨髓动员到外周血参与损伤血管的修复及血管的新生。 近年来的研究显示,内皮祖细胞在心脑血管疾病、外周血管、肿瘤血管形成及创伤愈合等方面均发挥重要作用，并为缺血性疾病的研究治疗提供了新思路。近年来，EPCs生物学特性和治疗作用的研究成为这一领域新的热点。 目前研究表明，内皮祖细胞主要来源于骨髓、外周血。 Introduction Methods Results Figure 1.EPC transplantation improved nerve function in diabetic mice. Results Figure 2.EPC transplantation increased blood perfusion in diabetic nerves. Results Figure 3. EPC transplantation restored neural vascularity in DN. Results Figure 4. Preferential and sustained engraftment of Transplanted EPCs in sciatic nerves. Results Figure 5. Localization of transplanted EPCs along the vasa nervorum and transdifferentiation of EPCs into endothelial cells in nerves. Results Figure 6. EPC transplantation increased Schwann cell and endothelial cell proliferation. Results Figure 7. EPC transplantation decreased apoptosis. Results Figure 8. EPC transplantation increased multiple angiogenic and neurotrophic factors. Conclusion We demonstrate for the first time that bone marrow-derived EPCs could reverse various manifestations of diabetic neuropathy. These therapeutic effects were mediated by direct augmentation of neovascularization in peripheral nerves through long-term and preferential engraftment of EPCs in nerves and particularly vasa nervorum and their paracrine effects. These findings suggest that EPC transplantation could represent an innovative therapeutic optio