骨骨髓来源的生物能量学和功能后果多能祖细胞移植与postinfarction心脏左心室重构。
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王曾L时,胡锦涛Q, X, Mansoor,李J, Feygin J,张G, Suntharalingam P,布泽尔年代,Mhashilkar,帕内塔CJ, Swingen C,院长R,从啊,贝奇RJ, Verfaillie厘米,张J
骨骨髓来源的生物能量学和功能后果多能祖细胞移植与postinfarction心脏左心室重构。
循环。2007年4月10日,115 (14):1866 - 75。Epub 2007年3月26日。
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17389266 (在PubMed]
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背景:本研究调查是否附着骨骨髓来源干细胞的移植,称为pMultistem,诱发新血管形成和稳定生物能量学和收缩功能的心肌细胞再生梗死区和边界区(BZ)在冠状动脉闭塞。方法和结果:左冠状动脉前降永久闭塞引起的猪左心室重塑的射血分数减少55 + / 30 + -5.6% / -5.4%(核磁共振成像)。左冠状动脉前降4周后闭塞,BZ心肌展示了深刻的生物能量学异常,显著降低subendocardial磷酸肌酸/ ATP (31 p磁共振光谱学;1.06 + / - -0.30在梗塞的心中(n = 9)和1.90 + / - -0.15在正常的心(n = 8;P < 0.01)。这个异常是显著提高同种异体移植的pMultistem细胞(subendocardial磷酸肌酸/ ATP 1.34 + / - -0.29;n = 7;P < 0.05)。肌酸kinase-mt BZ蛋白表达和肌酸kinase-m亚型的人数明显减少梗塞的心里但显著恢复细胞移植。MRI显示梗塞区收缩期增厚部分从收缩压明显改善“膨胀”与心肌梗死治疗动物活动增厚(19.7 + / - -9.8%,P < 0.01),而左心室射血分数提高到42.0 + / - -6.5% (P < 0.05和心肌梗死)。 Only 0.35+/-0.05% donor cells could be detected 4 weeks after left anterior descending artery ligation, independent of cell transplantation with or without immunosuppression with cyclosporine A (with cyclosporine A, n=6; no cyclosporine A, n=7). The fraction of grafted cells that acquired an endothelial or cardiomyocyte phenotype was 3% and approximately 2%, respectively. Patchy spared myocytes in the infarct zone were found only in pMultistem transplanted hearts. Vascular density was significantly higher in both BZ and infarct zone of cell-treated hearts than in untreated myocardial infarction hearts (P<0.05). CONCLUSIONS: Thus, allogeneic pMultistem improved BZ energetics, regional contractile performance, and global left ventricular ejection fraction. These improvements may have resulted from paracrine effects that include increased vascular density in the BZ and spared myocytes in the infarct zone.