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Cell surface markers for immunophenotyping human pluripotent stem cell-derived cardiomyocytes

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Abstract

Human pluripotent stem cells (hPSC) self-renew and represent a potentially unlimited source for the production of cardiomyocytes (CMs) suitable for studies of human cardiac development, drug discovery, cardiotoxicity testing, and disease modelling and for cell-based therapies. However, most cardiac differentiation protocols yield mixed cultures of atrial-, ventricular-, and pacemaker-like cells at various stages of development, as well as non-CMs. The proportions and maturation states of these cell types result from disparities among differentiation protocols and time of cultivation, as well as hPSC reprogramming inconsistencies and genetic background variations. The reproducible use of hPSC-CMs for research and therapy is therefore limited by issues of cell population heterogeneity and functional states of maturation. A validated method that overcomes issues of cell heterogeneity is immunophenotyping coupled with live cell sorting, an approach that relies on accessible surface markers restricted to the desired cell type(s). Here we review current progress in unravelling heterogeneity in hPSC-cardiac cultures and in the identification of surface markers suitable for defining cardiac identity, subtype specificity, and maturation states.

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Funding

This work was supported by funding from the ‘Improvement on Competitiveness in Hiring New Faculties’ Funding Scheme and the Direct Grant from the Chinese University of Hong Kong to E.N.P.

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  1. Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA

    Kenneth R. Boheler

  2. Department, of Medicine and Therapeutics, Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, HKSAR, China

    Ellen Ngar-Yun Poon

  3. Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong, HKSAR, China

    Ellen Ngar-Yun Poon

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This article is published as part of the Special Issue on Recent Progress with hPSCs for Drug Discovery, Organoids, Disease Models, and Cardiac Repair.

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Boheler, K.R., Poon, E.NY. Cell surface markers for immunophenotyping human pluripotent stem cell-derived cardiomyocytes. Pflugers Arch - Eur J Physiol 473, 1023–1039 (2021). https://doi.org/10.1007/s00424-021-02549-8

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