Islet-1诱导MSCs特化心肌细胞的电生理构建与能量代谢重塑调控

研究表明，间充质干细胞（MSCs）可诱导分化为心肌样细胞，但具备电生理功能是临床应用的关键。心肌细胞中能量代谢影响离子通道、泵和交换器的结构-功能，其改变受过氧化酶受体共激活因子PGC-1α调控。本课题组系列研究发现Islet-1诱导分化的细胞具有心肌特异性离子通道基因表达和钠、钾、钙离子电流，但功能不完全；成熟的心肌细胞线粒体活跃，且与PGC-1α表达相关。结合文献分析和课题组前期研究，我们提出科学假设：Islet-1诱导MSCs向心肌细胞特化过程中，通过对PGC-1α进行乙酰化/甲基化修饰，促进细胞组织特异性结构完整、线粒体结构功能成熟、能量供应充足，实现正常的电生理功能。该研究将在MSCs心肌细胞特化中靶点干预的基础上，阐释能量代谢重塑与电生理构建关联机制，为MSCs诱导分化为具有电生理功能的心肌细胞，用于修复受损心肌组织，恢复功能，以及干细胞相关应用研究提供理论基础和科学模式。

According to research, mesenchymal stem cells (MSCs) can be induced into cardiomyocyte-like cells, and its electrophysiological functions is critical for clinical applications. Energy metabolism in cardiomyocytes affects the structure and function of ion-channels, pumps, and exchangers, and its alteration is regulated by the peroxidase receptor coactivator PGC-1α. Our research team found that the cardiomyocyte-like cells induced by transfecting Islet-1 from MSCs, were capable to express myocardial-specific ion channel gene, as well as myocardial-similar sodium, potassium, and calcium channel currents, although those currents were not strong enough; the mitochondria in mature cardiomyocytes were active, associated with PGC-1α expression. With the acknowledge of current reports and our previous research, the scientific hypothesis is proposed: during the process of MSCs’ cardiomyocyte specialization induced by Islet-1, interfering PGC-1α acetylation/methylation modification may bring the differentiated cells a complete tissue-specific structure, a sufficient energy supplement and a perfect electrophysiological functions. This research will fully reveal the selection of intervention targets and the mechanisms of energy metabolism remodeling and electrophysiological construction, to provide MSCs-induced cardiomyocytes better electrophysiological function, which can be used to repair damaged myocardial tissue and restore function, as well as a research pattern on stem cell application.