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Cardiomyocyte Maturation–the Road is not Obstructed

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Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent one of the most promising ways to treat cardiovascular diseases. High-purity cardiomyocytes (CM) from different cell sources could be obtained at present. However, the immature nature of these cardiomyocytes hinders its further clinical application. From immature to mature state, it involves structural, functional, and metabolic changes in cardiomyocytes. Generally, two types of culturing (2D and 3D) systems have been reported to induce cardiomyocyte maturation. 2D culture mainly achieves the maturation of cardiomyocytes through long-term culture, co-culture, supplementation of small molecule compounds, and the application of biophysical cues. The combined use of biomaterial's surface topography and biophysical cues also facilitates the maturation of cardiomyocytes. Cardiomyocyte maturation is a complex process involving many signaling pathways, and current methods fail to fully reproduce this process. Therefore, analyzing the signaling pathway network related to the maturation and producing hPSC-CMs with adult-like phenotype is a challenge. In this review, we summarized the structural and functional differences between hPSC-CMs and mature cardiomyocytes, and introduced various methods to induce cardiomyocyte maturation.

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Funding

This study was supported by the National Key R&D Program of China (2021YFA1101902), the National Natural Science Foundation of China (82170364, 91949111, 81970223, 82003756), Jiangsu Province’s Key Discipline/Laboratory of Medicine (XK201118) and Introduction Project of Clinical Medicine Expert Team for Suzhou (SZYJTD201704).

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    1. Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, 215000, China

      Yaning Wang, Miao Yu, Kaili Hao, Wei Lei, Mingliang Tang & Shijun Hu

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    1. Yaning Wang
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    2. Miao Yu
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    3. Kaili Hao
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    4. Wei Lei
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    YW, MY and KH wrote the manuscript and contributed equally to this work. LW revised the manuscript. MT and SH wrote and revised the manuscript.

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    Correspondence to Mingliang Tang or Shijun Hu.

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    Yaning Wang, Miao Yu, and Kaili Hao are co-first authors and contribute equally to this work

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    Wang, Y., Yu, M., Hao, K. et al. Cardiomyocyte Maturation–the Road is not Obstructed. Stem Cell Rev and Rep 18, 2966–2981 (2022). https://doi.org/10.1007/s12015-022-10407-y

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