摘要
目的:了解国内外在胚胎干细胞向心肌细胞分化的机理及其应用潜能等方面的研究现状。资料来源:应用计算机检索Medline,检索时间为1997/2005,检索词限定为“embryonicstemcell,cardiomyocyte/cardiacmyocyte,differentia-tion”,并限定语言种类为英文。资料选择:对所检索到的文献进行初审,纳入标准:符合胚胎干细胞向心肌细胞分化的文章。排除标准:重复性研究。资料提炼:共查找文献200余篇,筛选出26篇。资料综合:收集到多篇关于胚胎干细胞分化为心肌细胞的文章,从最初获得胚胎干细胞源性心肌细胞的实验方法的建立到在单细胞水平对胚胎干细胞源性心肌细胞进行电生理研究。进一步,很多研究者从转录因子的角度研究了控制心脏发育的转录因子在胚胎干细胞向心肌细胞分化过程中的表达,研究表明心脏转录因子GATA4、肌细胞增强因子2C和NKx2.5控制着心脏基因的表达,它们在心脏发生过程中发挥重要的转录调控作用。研究同时发现,钙调神经磷酸酶信号通路、MAPK信号通路以及其他信号通路参与了心肌细胞分化的调节。此外,从胚胎干细胞纯化分化的心肌细胞用于治疗心肌梗死亦是一个关键问题。结论:当胚胎干细胞以胚小体的形式在没有白血病抑制因子的条件下培养时,一些干细胞可以分化成心肌细胞。干细胞来源的心肌细胞表达一些收缩蛋白,如MHC和肌球蛋白轻链-2V。转录因子GATA4、肌细胞增强因子2C和NKx2.5在心肌细胞分化中发挥重要作用,并且可以触发特异基因如α-肌动蛋白、MHC和肌球蛋白轻链-2V的表达,然而,胚胎细胞向心肌细胞分化的分子机制还有待进一步研究,鉴别出促进心脏分化的因子是研究心脏分化的基础所在。
OBJECTIVE: To investigate the research condition of mechanism of cardiomyocytes differentiation from embryonic stem (ES) cells and the application potency of ES cells at home and abroad. DATA SOURCES: We searched in Medline database from 1997 to 2005 with the key words of "embryonic stem cell ,cardiomyocyte/cardiac myocyte,differentiation" in English. STUDY SELECTION: The retrieved data were selected primarily. Inclusive criterion: articles of differentiation into cardiomyocytes from ES cells. Exclusive criterion: the articles of repetitive research were excluded. DATA EXTRACTION: Totally more than 200 articles were researched, and 26 were included. DATA SYNTHESIS: Some articles of differentiation of ES cells into cardiomyocytes from the construction of primarily experimental methods of cardiomyocytes differentiation from ES cells to electrophysiologic study of ES cells-derived cardiomyocytes in monoplast level were collected. Furthermore, many investigators studied the expression of transcription factors that controlled cardio development in the differentiation of ES cells to cardiomyocytes from the angle of transcription factors. Cardiac transcription factors GATA4, MEF2C and NKx2.5 had been reported to control a cardiac gene program and thus to play a crucial role in transcriptional regulation during cardiogenesis. Meanwhile, calcineurin, MAPKs and other signaling pathways were also involved in the adjustment of cardiomyocyte differentiation. In addition, the purity of differentiated ES-derived cardiomyocyte cultures for myocardial infarction was a key issue. CONCLUSION: When ES cells are cultured within EBs and in the absence of leukemia inhibitory factor (LIF), some of them can differentiate into cardiomyocytes. ES-derived cardiomyocytes express characteristic contractile proteins, such as MHC and myosin light chain (MLC)-2V. Transcription factors, including GATA4, MEF2C and NKx2.5, play a crucial role in the cardioblast differentiation and trigger the expression of specific g
出处
《中国临床康复》
CSCD
北大核心
2006年第45期213-217,共5页
Chinese Journal of Clinical Rehabilitation
基金
国家自然科学基金(30370582,30440065,30572082)
北京自然科学基金(7052059)~~