骨髓源性多能成体祖细胞向起搏细胞的诱导分化

发布时间：2018-01-03 08:21

本文关键词：骨髓源性多能成体祖细胞向起搏细胞的诱导分化　出处：《第二军医大学》2010年博士论文　论文类型：学位论文

【摘要】： 生物心脏起搏器是心血管领域研究热点问题。当前构建生物心脏起搏器主要包括基因转染、细胞移植和组织工程化起搏、传导组织移植三种方法。基因转染普遍存在外源基因在体内缺乏长期稳定表达、难以有效调控等缺点。细胞移植,组织工程化起搏、传导组织移植可以避免通过转染基因建立生物起搏器的缺点。但是,目前在心脏生物起搏器研究中探讨的组织细胞(窦房结细胞、幼稚心肌细胞、基因转染的心肌细胞等)、胚胎干细胞、间充质干细胞,均有其目前无法克服的弊端,寻找新的种子细胞,是心脏生物起搏器研究的当务之急。本研究拟采用条件培养、与起搏细胞联合培养等方法,探讨将骨髓多能成体祖细胞诱导分化为起搏细胞的可能性,旨在为心脏生物起搏器的构建提供一种来源丰富、无排斥反应、活性好的种子细胞。研究发现,5.氮杂胞苷+内皮素-1、窦房结细胞培养液等条件培养可使MAPCs表达起搏离子通道,与窦房结细胞共培养能将MAPCs诱导分化为起搏样细胞；该细胞体外具有驱动心肌跳动的起搏活性。
[Abstract]:Biological pacemaker is a hot issue in the field of cardiovascular research. Currently, the construction of biological pacemaker mainly includes gene transfection, cell transplantation and tissue engineering pacing. Three methods of conducting tissue transplantation. Gene transfection has many shortcomings such as lack of long-term stable expression of exogenous gene in vivo, difficulty in effective regulation, cell transplantation and tissue engineering pacing. Conducting tissue transplantation can avoid the disadvantage of establishing biological pacemaker by gene transfection. However, tissue cells (sinoatrial node cells, immature cardiomyocytes) are studied in the study of cardiac biological pacemakers. Gene transfection of cardiac myocytes, embryonic stem cells, mesenchymal stem cells, all have their current defects can not be overcome, looking for new seed cells. It is an urgent task for the study of cardiac biological pacemakers. This study aims to explore the possibility of inducing and differentiating bone marrow pluripotent adult progenitor cells into pacemaker cells by means of conditioned culture and co-culture with pacemaker cells. In order to provide a rich source, no rejection, good activity of seed cells for the construction of cardiac biological pacemakers. 5. Azacytidine endothelin-1. MAPCs expression of pacemaker ion channel could be induced by sinoatrial node cell culture medium, and MAPCs could be induced to differentiate into pacemaker cells by co-culture with sinoatrial node cells. This cell has pacemaker activity to drive myocardial beating in vitro.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R329

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