摘要
目的采用2′脱氧5-氮杂胞苷(5-aza-CdR)诱导的骨髓间充质干细胞(MSCs)移植于心肌梗死后心力衰竭大鼠心肌中,评价其存活、分化及对心功能的影响。方法将经5-aza-CdR(0.3μmol/L)两次诱导,溴氮胞苷标记的第2代大鼠MSCs植入心肌梗死后10 d心力衰竭大鼠心肌疤痕中,同时以植入无血清培养基(DMEM)的大鼠为对照。移植前及移植后1月,通过检测左室射血分数(LVEF)等超声指标研究其对心功能的影响;应用双重免疫组化及电镜观察研究MSCs在心肌梗死区的存活和分化。结果移植后1月,MSCs组大鼠心功能[LVEF=(83±8)%,n=13]较DMEM组[LVEF=(47±12)%,n=12]显著改善(P<0.01);并且较移植前[LVEF=(64±10)%,n=13]也有显著提高(P<0.01)。移植的MSCs能在心肌及疤痕中存活,并向心肌细胞分化,Tropon inT及Connex-in43阳性。MSCs有肌丝形成,并与周围心肌细胞紧密连接,类似闰盘。结论经5-aza-CdR诱导的MSCs移植后1月,能在心肌梗死后心力衰竭大鼠心肌及疤痕中存活并向心肌细胞分化,且可改善大鼠的心功能。
AIM To investigate the survival and differentiation of 5-aza-2'-deoxycytidine (5-aza-CdR) induced mesenchymal stem cells (MSCs) in infracted myocardium and their effect on infarction-induced heart failure in rats. METHODS Two-passaged and labeled by bromodeoxyuridine, were transplan rat MSCs, induced twice by 5-aza-CdR (0.3 μmol/L) ted into the ventricutar Scar tissues of rats in the model of infarction-induced heart failure. The rats receiving serum-free medium (DMEM) injection were used as controls. One month after transplantation, the parameters of heart function, such as ejection fraction (LVEF), were examined by echocardiography and the survival and differentiation of the transplanted MSCs were observed by double-lable immunohistochemistry and electronic microscope. RESULTS One month after transplantation, the EF value of MSCs group[ LVEF = (83 ± 8 )%, n = 13 ] increased significantly compared to that of DMEM group [ LVEF = (47 ± 12 ) %, n = 12, P 〈 0.01 ] and improved compared to that before transplantation [ LVEF = (64 ± 10 )%, n = 13, P 〈 0.01 ]. The transplanted cells survived in myocardial scar and differentiated into cardiomyocytes with positive TroponinT and Connexin 43. Muscle silks formed in donor MSCs and the MSCs connected with native cardiomyocytes compactly like intercalated disks. CONCLUSION One month after transplantation, 5-aza-CdR induced MSCs can survive in the infracted scar of rats and possess some characters of cardiomyocytes. The 5-aza-CdR induced MSCs improve the heart function of infarction-induced heart failure in rats.
出处
《心脏杂志》
CAS
2006年第2期138-142,共5页
Chinese Heart Journal
基金
上海市自然科学基金项目资助(No.02ZB14038)
关键词
骨髓间充质干细胞
细胞移植
心力衰竭
mesenchymal stem cells
cell transplantation
heart failure