骨髓源性多能成體祖細胞向起搏細胞的誘導分化
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本文關鍵詞:骨髓源性多能成體祖細胞向起搏細胞的誘導分化 出處:《第二軍醫(yī)大學》2010年博士論文 論文類型:學位論文
更多相關文章: 生物起搏器 成體多能祖細胞 竇房結 共培養(yǎng) 起搏基因 離子通道
【摘要】: 生物心臟起搏器是心血管領域研究熱點問題。當前構建生物心臟起搏器主要包括基因轉染、細胞移植和組織工程化起搏、傳導組織移植三種方法。基因轉染普遍存在外源基因在體內(nèi)缺乏長期穩(wěn)定表達、難以有效調控等缺點。細胞移植,組織工程化起搏、傳導組織移植可以避免通過轉染基因建立生物起搏器的缺點。但是,目前在心臟生物起搏器研究中探討的組織細胞(竇房結細胞、幼稚心肌細胞、基因轉染的心肌細胞等)、胚胎干細胞、間充質干細胞,均有其目前無法克服的弊端,尋找新的種子細胞,是心臟生物起搏器研究的當務之急。本研究擬采用條件培養(yǎng)、與起搏細胞聯(lián)合培養(yǎng)等方法,探討將骨髓多能成體祖細胞誘導分化為起搏細胞的可能性,旨在為心臟生物起搏器的構建提供一種來源豐富、無排斥反應、活性好的種子細胞。研究發(fā)現(xiàn),5.氮雜胞苷+內(nèi)皮素-1、竇房結細胞培養(yǎng)液等條件培養(yǎng)可使MAPCs表達起搏離子通道,與竇房結細胞共培養(yǎng)能將MAPCs誘導分化為起搏樣細胞;該細胞體外具有驅動心肌跳動的起搏活性。
[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.
【學位授予單位】:第二軍醫(yī)大學
【學位級別】:博士
【學位授予年份】:2010
【分類號】:R329
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