Kazakov Andrey, Meier Timo, Werner Christian, Hall Rabea, Klemmer Birgit, Körbel Christina, Lammert Frank, Maack Christoph, Böhm Michael, Laufs Ulrich
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universität des Saarlandes, Kirrberger Straße, Gebäude 40, 66421 Homburg/Saar, Germany.
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universität des Saarlandes, Kirrberger Straße, Gebäude 40, 66421 Homburg/Saar, Germany.
Stem Cell Res. 2015 Nov;15(3):700-711. doi: 10.1016/j.scr.2015.10.017. Epub 2015 Oct 28.
To investigate the effect of resident cardiac stem cells (RCSC) on myocardial remodeling, c-kit(+) RCSC were isolated from hearts of C57Bl/6-Tg (ACTb-EGFP)1Osb/J mice expressing green fluorescent protein and expanded in vitro. C57/Bl6N wildtype mice were subjected to transverse aortic constriction (TAC, 360 μm) or sham-operation. 5 × 10(5) c-kit(+) RCSC or c-kit(-) cardiac cells or cell buffer were infused intravenously 24 h post-surgery (n = 11-24 per group). Hypoxia-inducible factor-1α-mRNA in left ventricles of TAC mice was enhanced 24 h after transplantation. 35 days post-TAC, the density of c-kit(+) RCSC in the myocardium was increased by two-fold. Infusion of c-kit(+) resident cardiac stem cells post-TAC markedly reduced myocardial fibrosis and the expression of collagen Iα2 and connective tissue growth factor. Infusion of c-kit(-) cardiac cells did not ameliorate cardiac fibrosis. In parallel, expression of pro-angiogenic mediators (FGFb, IL-4, IL-6, TGFß, leptin) and the density of CD31(+) and CD31(+) GFP(+) endothelial cells were increased. Transplantation reduced brain- and atrial natriuretic peptides and the cardiomyocyte cross-sectional area. Infusion of c-kit(+) resident cardiac stem reduced the rate of apoptosis and oxidative stress in cardiomyocytes and in non-cardiomyocyte cells.
为研究内源性心脏干细胞（RCSC）对心肌重塑的影响，从表达绿色荧光蛋白的C57Bl/6-Tg (ACTb-EGFP)1Osb/J小鼠心脏中分离出c-kit(+) RCSC并在体外进行扩增。将C57/Bl6N野生型小鼠进行横向主动脉缩窄（TAC，360μm）或假手术。术后24小时静脉注射5×10(5)个c-kit(+) RCSC或c-kit(-)心脏细胞或细胞缓冲液（每组n = 11 - 24）。TAC小鼠左心室中的缺氧诱导因子-1α-mRNA在移植后24小时增强。TAC术后35天，心肌中c-kit(+) RCSC的密度增加了两倍。TAC后输注c-kit(+)内源性心脏干细胞显著减少了心肌纤维化以及Iα2型胶原蛋白和结缔组织生长因子的表达。输注c-kit(-)心脏细胞并未改善心脏纤维化。同时，促血管生成介质（FGFb、IL-4、IL-6、TGFß、瘦素）的表达以及CD31(+)和CD31(+) GFP(+)内皮细胞的密度增加。移植降低了脑钠肽和心房钠尿肽以及心肌细胞横截面积。输注c-kit(+)内源性心脏干细胞降低了心肌细胞和非心肌细胞中的细胞凋亡率和氧化应激。
