應用不同方法體外誘導P19細胞心肌細胞分化的研究
發(fā)布時間：2019-02-16 11:27
【摘要】： 一般認為成年哺乳動物的心肌細胞系終末分化細胞,無或僅有有限的再生修復能力,一旦損傷,壞死的心肌只能由無功能的纖維瘢痕組織代替。心肌缺血引發(fā)的心肌細胞大量不可逆性缺失、存活的功能性細胞數(shù)量下降等多種因素最終將導致心力衰竭的發(fā)生,這已成為心血管疾病死亡的主要原因。盡管近些年有研究表明,成體心臟內(nèi)有可以增殖的心肌干細胞存在,但由于其增殖潛能有限,不足以修復受損的心肌組織。目前,心臟移植成為治療心肌壞死疾病的一有效途徑,但由于供體短缺、復雜的免疫反應及高額的治療費用限制了其治療作用。因此,研究者及臨床都在尋找新的有效的治療方案。細胞移植為病損心肌的細胞修復及心功能恢復提供了一種全新的治療方案�？茖W家先后應用多種類型的細胞,包括胎兒和新生兒心肌細胞、骨骼肌衛(wèi)星細胞、平滑肌細胞、成纖維細胞及骨髓來源的細胞進行細胞移植治療心肌梗塞的動物模型試驗,并已取得了較好的進展。但由于細胞來源有限,同時免疫排斥反應等造成移植細胞的大量死亡,因此如何獲得大量細胞進行移植以保證足夠量的細胞存活或改善移植細胞的存活是目前面臨的主要問題。 胚胎畸瘤細胞(embryonal carcinoma cells, EC)細胞與胚胎干細胞(embryonic stem cells, ES)在分化潛能、超微結(jié)構(gòu)、細胞表面抗原和生化特性等方面具有相似性,同時與ES細胞相比,EC細胞在無需飼養(yǎng)層和LIF (leukemia inhibitory factory, LIF)條件下培養(yǎng)即可保持未分化狀態(tài),更易于培養(yǎng),且易于進行基因操作,而且通過分化培養(yǎng)過程EC細胞可從惡性表型轉(zhuǎn)化為非惡性表型,因此EC細胞的研究應用日益受到廣大研究者的青睞。P19EC細胞系是McBurney等從C3H/He小鼠畸胎瘤中分離得到的具有多分化潛能的胚胎性干細胞,其在體外培養(yǎng)中單層生長無需飼養(yǎng)層即可迅速大量擴增,經(jīng)多次傳代仍保持胚胎干細胞特有標記,如表面糖蛋白SSEA-1及轉(zhuǎn)錄因子Oct-3等。在體外,通過條件培養(yǎng)P19細胞被誘導為包括心肌細胞、骨骼肌細胞、神經(jīng)元等多種類型的細胞,且分化過程類似
[Abstract]:It is generally believed that adult mammalian myocardial cell line terminal differentiation cells have no or only limited regeneration and repair ability. Once damaged, the necrotic myocardium can only be replaced by nonfunctioning fibrous scar tissue. A large number of irreversible loss of myocardial cells caused by myocardial ischemia and a decrease in the number of viable functional cells will eventually lead to heart failure which has become the main cause of death of cardiovascular disease. Although recent studies have shown that there are proliferative myocardial stem cells in adult hearts, but due to their limited proliferative potential, it is not sufficient to repair damaged myocardial tissue. At present, heart transplantation has become an effective way to treat myocardial necrotic diseases. However, due to the shortage of donors, complex immune response and high treatment costs limit its therapeutic effect. Therefore, researchers and clinical are looking for new and effective treatment. Cell transplantation provides a new therapy for the repair of damaged myocardium and the recovery of cardiac function. Scientists have used a variety of cell types, including fetal and neonatal cardiomyocytes, skeletal muscle satellite cells, smooth muscle cells, fibroblasts and bone marrow-derived cells, to carry out an animal model study of cell transplantation in the treatment of myocardial infarction. Good progress has been made. However, due to the limited source of cells and immune rejection, so how to obtain a large number of cells for transplantation to ensure a sufficient number of cells to survive or improve the survival of transplanted cells is the main problem. The differentiation potential, ultrastructure, cell surface antigen and biochemical characteristics of embryonic teratoma cell (embryonal carcinoma cells, EC) cells were similar to those of embryonic stem cell (embryonic stem cells, ES) cells, and compared with those of ES cells. EC cells could be cultured in undifferentiated condition without feeding layer and LIF (leukemia inhibitory factory, LIF). It was easy to culture and gene manipulation, and EC cells could be transformed from malignant phenotype to non-malignant phenotype through differentiation and culture. Therefore, the research and application of EC cells are increasingly favored by many researchers. P19EC cell lines are embryonic stem cells with multiple differentiation potential obtained from teratoma of C3H/He mice such as McBurney. In vitro culture, monolayer growth can be expanded rapidly without feeding layer, and the specific markers of embryonic stem cells, such as surface glycoprotein SSEA-1 and transcription factor Oct-3, can be maintained after multiple passages. In vitro, P19 cells in conditioned culture were induced to include cardiomyocytes, skeletal muscle cells, neurons and other types of cells. The differentiation process was similar to that of P19 cells.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R329
本文編號：2424398
[Abstract]:It is generally believed that adult mammalian myocardial cell line terminal differentiation cells have no or only limited regeneration and repair ability. Once damaged, the necrotic myocardium can only be replaced by nonfunctioning fibrous scar tissue. A large number of irreversible loss of myocardial cells caused by myocardial ischemia and a decrease in the number of viable functional cells will eventually lead to heart failure which has become the main cause of death of cardiovascular disease. Although recent studies have shown that there are proliferative myocardial stem cells in adult hearts, but due to their limited proliferative potential, it is not sufficient to repair damaged myocardial tissue. At present, heart transplantation has become an effective way to treat myocardial necrotic diseases. However, due to the shortage of donors, complex immune response and high treatment costs limit its therapeutic effect. Therefore, researchers and clinical are looking for new and effective treatment. Cell transplantation provides a new therapy for the repair of damaged myocardium and the recovery of cardiac function. Scientists have used a variety of cell types, including fetal and neonatal cardiomyocytes, skeletal muscle satellite cells, smooth muscle cells, fibroblasts and bone marrow-derived cells, to carry out an animal model study of cell transplantation in the treatment of myocardial infarction. Good progress has been made. However, due to the limited source of cells and immune rejection, so how to obtain a large number of cells for transplantation to ensure a sufficient number of cells to survive or improve the survival of transplanted cells is the main problem. The differentiation potential, ultrastructure, cell surface antigen and biochemical characteristics of embryonic teratoma cell (embryonal carcinoma cells, EC) cells were similar to those of embryonic stem cell (embryonic stem cells, ES) cells, and compared with those of ES cells. EC cells could be cultured in undifferentiated condition without feeding layer and LIF (leukemia inhibitory factory, LIF). It was easy to culture and gene manipulation, and EC cells could be transformed from malignant phenotype to non-malignant phenotype through differentiation and culture. Therefore, the research and application of EC cells are increasingly favored by many researchers. P19EC cell lines are embryonic stem cells with multiple differentiation potential obtained from teratoma of C3H/He mice such as McBurney. In vitro culture, monolayer growth can be expanded rapidly without feeding layer, and the specific markers of embryonic stem cells, such as surface glycoprotein SSEA-1 and transcription factor Oct-3, can be maintained after multiple passages. In vitro, P19 cells in conditioned culture were induced to include cardiomyocytes, skeletal muscle cells, neurons and other types of cells. The differentiation process was similar to that of P19 cells.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R329
【參考文獻】
相關(guān)期刊論文 前5條
1 鄭斌,溫進坤,韓梅;LIM蛋白家族的研究進展[J];生理科學進展;2002年04期
2 陳光慧,周子振,張繼峰,陳春蕾,李凌松,關(guān)新元,周愛儒,馬大龍,湯健,mail.bjmu.edu.cn;應用三元遞減法篩選特異性心臟生長相關(guān)基因[J];中國生物化學與分子生物學報;2000年03期
3 劉進軍;成年心肌細胞增生的研究進展[J];國外醫(yī)學(生理、病理科學與臨床分冊);2003年03期
4 劉蘭英,楊琨,朱振宇,劉玉川,余細勇,銀巍,湯建,馬澗泉,顧軍;胚胎干細胞體外分化為心肌細胞誘導因素的探討[J];中國病理生理雜志;2000年05期
5 方天翎,閔軍,鄧小耿,錢世潂,褚忠華,陳亞進,邵靜,魏菁,陳積圣;肝細胞生長因子誘導骨髓間質(zhì)干細胞分化為心肌細胞[J];中國病理生理雜志;2004年07期
，本文編號：2424398
本文鏈接：http://sikaile.net/yixuelunwen/binglixuelunwen/2424398.html
最近更新
教材專著
