Connexin 43 gene-modified BMSCs for treating myocardial infarction

LI Xiao-hong; JIANG Xue-yan; ZHU Jie-ning; MAI Li-ping; XIAO Dingzhang; FU Yong-heng; KUANG Su-juan; ZHANG Guang-feng; YU Xi-yong

摘要：Background Stem cells have multilineage differentiation capacity, which makes bone marrow mesenchymal stem cells (BMSCs) derived relatively easy and provides a pronusing alternative treatment for myocardial infarction (Ml). The in vivo cardiac differentiation and functional effects of unmodified BMSCs after Ml are controversial. Poor moderate survival benefits of BMSCs-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted BMSCs in the infarcted myocardium. This study was to investigate whether connexin43 (Cx43) modified BMSCs improve therapeutic efficacy in Ml. Methods Lentivirus mediated Cx43 gene was transfected into human BMSCs. Flowcytometry was used to detect cell surface markers of BMSCs before and after Cx43 transfection. Cx43expression levels were detected by fluorescent nucroscope and western blotting. Post-MI intramyocardial injection of I x 106 stem cells was compared with injection of medium alone. Heart function was detected by echocardiography. Results Cx43 of BMSCs could be effectively overexpressed by lentivirus mediated gene transfection. Flowcytometry showed that after Cx43 overexpression, the surface markers of BMSCs were greatly decreased. Immunofluorescent microscopy revealed GFP-posotive transplanted BMSCs among the Ml area. The Cx43-BMSCs-treated heart, assessed by echocardiography, improved ejection fraction compared with PBS-and mock-BMSCs-treated hearts (P < 0.01). Conclusions Lenti-Cx43 can be effectively transfected into BMSCs. Cx43 may act as a potential target for improving the therapeutic efficacy of BMSCs in ischaenuc heart disease.