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微尺度凹槽通过瞬时受体电位通道 (TRP 通道) 调节 hPSC-CMs 的成熟发育。

Microscale grooves regulate maturation development of hPSC-CMs by the transient receptor potential channels (TRP channels).

机构信息

Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

出版信息

J Cell Mol Med. 2021 Apr;25(7):3469-3483. doi: 10.1111/jcmm.16429. Epub 2021 Mar 10.

Abstract

The use of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Micro-scaled grooves can promote the maturation of cardiomyocytes by aligning them in order, but the mechanism of cardiomyocytes alignment has not been studied. From the level of calcium activity, gene expression and cell morphology, we verified that the W20H5 grooves can effectively promote the maturation of cardiomyocytes. The transient receptor potential channels (TRP channels) also play an important role in the maturation and development of cardiomyocytes. These findings support the engineered hPSC-CMs as a powerful model to study cardiac disease mechanism and partly mimic the myocardial morphological development. The important role of the TRP channels in the maturation and development of myocardium is first revealed.

摘要

人多能干细胞衍生的心肌细胞(hPSC-CMs)在药物发现和心脏疾病机制研究中的应用受到细胞不成熟的限制。微尺度凹槽可以通过有序排列来促进心肌细胞的成熟,但心肌细胞排列的机制尚未研究。从钙活性、基因表达和细胞形态水平上,我们验证了 W20H5 凹槽可以有效地促进心肌细胞的成熟。瞬时受体电位通道(TRP 通道)在心肌细胞的成熟和发育中也起着重要作用。这些发现支持工程化 hPSC-CMs 作为研究心脏疾病机制的有力模型,并在一定程度上模拟心肌形态发育。首次揭示了 TRP 通道在心肌成熟和发育中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3a/8034460/c222a71e4e9a/JCMM-25-3469-g003.jpg

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