You Position: Home > Paper
Effect of transplantation of embryonic stem cell-derived cardiomyocytes on cardiac function of rats with myocardial infarction
( views:166, downloads:20 )
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 9
- DOI:
- 10.3760/cma.j.issn.0254-1785.2007.09.004
- Key Word:
- 细胞移植;干细胞;心肌梗塞;心室重构;心室功能,左
Abstract： 目的 探讨小鼠胚胎干细胞(ES)分化的心肌细胞移植对SD大鼠心肌梗死后左心室重构及心功能的影响.方法 采用悬滴-悬浮培养法诱导ES分化形成拟胚体,其中包含有大量心肌细胞.将雄性SD大鼠冠状动脉左前降支结扎,制成急性心肌梗死模型,1周后再次开胸,实验组于梗死区域注入心肌细胞悬液150μl(含细胞5×105个),梗死对照组于梗死区域注入等体积细胞培养液,另设假手术组,不结扎冠状动脉.心肌梗死后1周和细胞移植后4周,采用超声心动图评价大鼠左心室形态和功能,用免疫荧光技术检测移植细胞的存活及其表型.结果 免疫荧光技术检测到分化的心肌细胞表达特异性转录因子α辅肌动蛋白、α肌球蛋白重链和肌钙蛋白Ⅰ;逆转录聚合酶链反应检测到有心肌特异性转录因子Nkx-2.5、GATA-4及α肌球蛋白重链基因的表达;膜片钳记录显示所得到的分化的心肌细胞包括窦房结样起搏细胞、心房样细胞和心室样细胞.细胞移植后4周,与梗死对照组相比,实验组左心室收缩末期容积和舒张末期容积均显著缩小,左心室前壁舒张末期厚度明显增加(P＜0.01),左室长轴缩短率显著升高(P＜0.01).心脏组织冰冻切片可见4,6-联脒-2-苯基吲哚标记的呈蓝色荧光的移植细胞核,移植细胞表达肌钙蛋白Ⅰ,移植细胞与受者的心肌细胞间有连接蛋白-43的表达.实验组中有2只(12.5%,2/16)出现了心脏畸胎瘤.结论 由胚胎干细胞分化的心肌细胞移植可逆转心肌梗死大鼠左心室重构,改善左心室功能.
- [1]Kishi Y,Hanazono Y,Terao K,etc.Improved safety of hematopoietic transplantation with monkey embryonic stem cells in the allogeneic setting.[J].2006,24(6).
- [2]Denice M, Hodgson,Atta, Behfar,Leonid V, Zingman,etc.Stable benefit of embryonic stem cell therapy in myocardial infarction.[J].2004,287(2).
- [3]Swijnenburg RJ,Klima U,Gold J,etc.Allopurinol/uricase and ibuprofen enhance engraftment of cardiomyocyte-enriched human embryonic stem cells and improve cardiac function following myocardial injury.[J].2006,29(1).
- [4]J A, Thomson,J, Itskovitz-Eldor,S S, Shapiro,etc.Embryonic stem cell lines derived from human blastocysts.[J].1998,282.
- [5]M J, Evans,M H, Kaufman.Establishment in culture of pluripotential cells from mouse embryos.[J].1981,292.
- [6]Hashimoto N,Sasai Y,Fukuda H,etc.Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation.[J].2006,24(3).
- [7]J A, Towbin,N E, Bowles.The failing heart.[J].2002,415(6868).
- [8]Binas B,Bader M,Lin X,etc.Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning.[J].2002,8(2).
- [9]Chen Y,Converso KL,Xiao YF,etc.Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells.[J].2003,125(2).
- [10]Kohn D,Halene S,Skelton D,etc.Immune response to green fluorescent protein: implications for gene therapy.[J].1999,6(7).
- [11]V A, Maltsev,A M, Wobus,J, Rohwedel,etc.Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents.[J].1994,75.