Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
PLoS One. 2012;7(4):e34960. doi: 10.1371/journal.pone.0034960. Epub 2012 Apr 4.
Mesenchymal stem cells (MSCs) are a potential source of material for the generation of tissue-engineered cardiac grafts because of their ability to transdifferentiate into cardiomyocytes after chemical treatments or co-culture with cardiomyocytes. Cardiomyocytes in the body are subjected to cyclic strain induced by the rhythmic heart beating. Whether cyclic strain could regulate rat bone marrow derived MSC (rBMSC) differentiation into cardiomyocyte-like lineage was investigated in this study. A stretching device was used to generate the cyclic strain for rBMSCs. Cardiomyogenic differentiation was evaluated using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry and western-blotting. The results demonstrated that appropriate cyclic strain treatment alone could induce cardiomyogenic differentiation of rBMSCs, as confirmed by the expression of cardiomyocyte-related markers at both mRNA and protein levels. Furthermore, rBMSCs exposed to the strain stimulation expressed cardiomyocyte-related markers at a higher level than the shear stimulation. In addition, when rBMSCs were exposed to both strain and 5-azacytidine (5-aza), expression levels of cardiomyocyte-related markers significantly increased to a degree suggestive of a synergistic interaction. These results suggest that cyclic strain is an important mechanical stimulus affecting the cardiomyogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells.
间充质干细胞（MSCs）是组织工程心脏移植物的潜在材料来源，因为它们在经过化学处理或与心肌细胞共培养后能够转分化为心肌细胞。体内的心肌细胞受到由有节奏的心跳引起的循环应变的影响。本研究旨在探讨循环应变是否能调节大鼠骨髓来源的间充质干细胞（rBMSC）向心肌细胞样谱系分化。使用拉伸装置产生 rBMSCs 的循环应变。通过定量实时逆转录聚合酶链反应（RT-PCR）、免疫细胞化学和 Western 印迹评估心肌生成分化。结果表明，适当的循环应变处理本身可以诱导 rBMSCs 的心肌生成分化，这通过 mRNA 和蛋白质水平上的心肌细胞相关标志物的表达得到证实。此外，暴露于应变刺激的 rBMSCs 表达的心肌细胞相关标志物水平高于剪切刺激。此外，当 rBMSCs 同时受到应变和 5-氮杂胞苷（5-aza）的刺激时，心肌细胞相关标志物的表达水平显著增加，表明存在协同作用。这些结果表明，循环应变是影响 rBMSCs 心肌生成分化的重要机械刺激。这为干细胞分化的机制研究提供了一个新的途径，并为获得更特化的分化细胞提供了一种新方法。
