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首页> 外文期刊>American Journal of Physiology >Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage
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Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage

机译:通过在细胞外基质上植入间充质干细胞以形成心脏谱系,可增强犬心脏机械功能的恢复

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Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage. Am J Physiol Heart Circ Physiol 295: H2257-H2263, 2008. First published October 3, 2008; doi:10.1152/ajpheart.00219.2008.~he need to regenerate tissue is paramount, especially for the heart that lacks the ability to regenerate after injury. The urinary bladder extracellular matrix (ECM), when used to repair a right ventricular defect, successfully regenerated some mechanical function. The objective of the current study was to determine whether the regenerative effect of ECM could be improved by seeding the patch with human mesenchymal stem cells (hMSCs) enhanced to differentiate down a cardiac linage. hMSCs were used to form three-dimensional spheroids. The expression of cardiac proteins was determined in cells exposed to the spheroid formation and compared with nonmanipulated hMSCs. To determine whether functional calcium channels were present, the cells were patch clamped. To evaluate the ability of these cells to regenerate mechanical function, the spheroids were seeded on ECM and then implanted into the canine heart to repair a full-thickness right ventricular defect. As a result, many of the cells spreading from the spheroids expressed cardiac-specific proteins, including sarcomeric a-ac-tinin, cardiotin, and atrial natriuretic peptide, as well as the cell cycle markers cyclin Dl and proliferating cell nuclear antigen. A calcium current similar in amplitude to that of ventricular myocytes was present in 16% of the cells. The cardiogenic cell-seeded scaffolds increased the regional mechanical function in the canine heart compared with the unmanipulated hMSC-seeded scaffolds. In addition, the cells prelabeled with fluorescent markers demonstrated myocyte-specific actinin staining with sarcomere spacing similar to that of normal myocytes. In conclusion, the spheroid-derived cells express cardiac-specific proteins and demonstrate a calcium current similar to adult ventricular myocytes. When these cells are implanted into the canine heart, some of these cells appear striated and mechanical function is improved compared with the unmanipulated hMSCs. Further investigation will be required to determine whether the increased mechanical function is due to a differentiation of the cardiogenic cells to myocytes or to other effects
机译:通过向细胞外基质贴上定型为心脏谱系的间充质干细胞,可增强犬心脏机械功能的恢复。 Am J Physiol Heart Circ Physiol 295:H2257-H2263,2008年。2008年10月3日首次发布; doi:10.1152 / ajpheart.00219.2008。〜他需要再生的组织至关重要,尤其是对于受伤后缺乏再生能力的心脏而言。膀胱细胞外基质(ECM)用于修复右心室缺陷时,成功地恢复了一些机械功能。当前研究的目的是确定是否可以通过在贴片上植入人间充质干细胞(hMSCs)增强其分化能力来改善ECM的再生能力,从而分化出心肌。 hMSC用于形成三维球体。测定暴露于球状体的细胞中心脏蛋白的表达,并与未处理的hMSCs进行比较。为了确定是否存在功能性钙通道,将细胞膜片钳。为了评估这些细胞再生机械功能的能力,将球状体接种在ECM上,然后植入犬心脏以修复全层右心室缺损。结果,从球体散布的许多细胞表达心脏特异性蛋白质,包括肌节蛋白α-ac-tinin,心磷脂和心钠素,以及细胞周期标志物cyclin D1和增殖性细胞核抗原。 16%的细胞中存在与心室肌细胞振幅相似的钙电流。与未操纵的hMSC种植支架相比,心源性种植细胞的支架增加了犬心脏的区域机械功能。另外,用荧光标记物预先标记的细胞表现出肌细胞特异性肌动蛋白染色,肌节间距与正常肌细胞相似。总之,球状细胞表达心脏特异性蛋白,并表现出类似于成人心室肌细胞的钙电流。当将这些细胞植入犬心脏时,其中的一些细胞呈横纹,与未处理的hMSC相比,其机械功能得到了改善。需要进一步研究以确定增加的机械功能是由于心源性细胞分化为心肌细胞还是其他作用所致

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