Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions

Xiaoping Bao, Xiaojun Lian, Timothy A. Hacker, Eric G. Schmuck, Tongcheng Qian, Vijesh J. Bhute, Tianxiao Han, Mengxuan Shi, Lauren Drowley, Alleyn T. Plowright, Qing Dong Wang, Marie Jose Goumans, Sean P. Palecek

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The epicardium contributes both multi-lineage descendants and paracrine factors to the heart during cardiogenesis and cardiac repair, underscoring its potential for use in cardiac regenerative medicine. Yet little is known about the cellular and molecular mechanisms that regulate human epicardial development and regeneration. Here, we show that the temporal modulation of canonical Wnt signalling is sufficient for epicardial induction from six different human pluripotent stem cell (hPSC) lines, including a WT1-2A-eGFP knock-in reporter line, under chemically defined, xeno-free conditions. We also show that treatment with transforming growth factor beta (TGF-β)-signalling inhibitors permitted long-term expansion of the hPSC-derived epicardial cells, resulting in more than 25 population doublings of WT1 + cells in homogenous monolayers. The hPSC-derived epicardial cells were similar to primary epicardial cells both in vitro and in vivo, as determined by morphological and functional assays, including RNA sequencing. Our findings have implications for the understanding of self-renewal mechanisms of the epicardium and for epicardial regeneration using cellular or small-molecule therapies.

Original languageEnglish (US)
Article number0003
JournalNature Biomedical Engineering
Volume1
Issue number1
DOIs
StatePublished - Jan 10 2017

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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    Bao, X., Lian, X., Hacker, T. A., Schmuck, E. G., Qian, T., Bhute, V. J., Han, T., Shi, M., Drowley, L., Plowright, A. T., Wang, Q. D., Goumans, M. J., & Palecek, S. P. (2017). Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nature Biomedical Engineering, 1(1), [0003]. https://doi.org/10.1038/s41551-016-0003