Effect of cellular and ECM aging on human iPSC-derived cardiomyocyte performance, maturity and senescence
Effect of cellular and ECM aging on human iPSC-derived cardiomyocyte performance, maturity and senescence
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DOI：
10.1016/j.biomaterials.2020.120554
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发表时间：
2021-01-01
期刊：
影响因子：
14
通讯作者：
Zorlutuna, Pinar
中科院分区：
文献类型：
--
作者：
Ozcebe, S. Gulberk;Bahcecioglu, Gokhan;Zorlutuna, Pinar
心血管疾病是世界范围内死亡的主要原因，其发生与年龄高度相关。然而，缺乏对心脏组织老化的认识是设计新疗法的主要障碍。在此，我们研究了细胞和心脏细胞外基质（ECM）老化对体外诱导多能干细胞（iPSC）衍生的心肌细胞状态、功能以及对心肌梗死（MI）模拟应激条件的反应的影响。在3周内，年轻ECM促进了年轻细胞的增殖和药物反应，并诱导衰老细胞重新进入细胞周期，并对应激具有保护作用。成人ECM可改善心功能，而老年ECM可加速衰老表型，损害细胞的心功能和应激防御机制。总之，我们对心脏老化有了全面的了解，并强调了细胞- ecm相互作用的重要性。这项研究首次探讨了细胞和环境老化对个体的影响，并确定了心脏老化时发生的生化变化。y
Cardiovascular diseases are the leading cause of death worldwide and their occurrence is highly associated with age. However, lack of knowledge in cardiac tissue aging is a major roadblock in devising novel therapies. Here, we studied the effects of cell and cardiac extracellular matrix (ECM) aging on the induced pluripotent stem cell (iPSC)-derived cardiomyocyte cell state, function, as well as response to myocardial infarction (MI)-mimicking stress conditions in vitro. Within 3-weeks, young ECM promoted proliferation and drug responsiveness in young cells, and induced cell cycle re-entry, and protection against stress in the aged cells. Adult ECM improved cardiac function, while aged ECM accelerated the aging phenotype, and impaired cardiac function and stress defense machinery of the cells. In summary, we have gained a comprehensive understanding of cardiac aging and highlighted the importance of cell-ECM interactions. This study is the first to investigate the individual effects of cellular and environmental aging and identify the biochemical changes that occur upon cardiac aging. y