Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


During cardiac development and morphogenesis, cardiac progenitor cells differentiate into cardiomyocytes that expand in number and size to generate the fully formed heart. Much is known about the factors that regulate initial differentiation of cardiomyocytes, and there is ongoing research to identify how these fetal and immature cardiomyocytes develop into fully functioning, mature cells. Accumulating evidence indicates that maturation limits proliferation and conversely proliferation occurs rarely in cardiomyocytes of the adult myocardium. We term this oppositional interplay the proliferation-maturation dichotomy. Here we review the factors that are involved in this interplay and discuss how a better understanding of the proliferation-maturation dichotomy could advance the utility of human induced pluripotent stem cell-derived cardiomyocytes for modeling in 3-dimensional engineered cardiac tissues to obtain truly adult-level function.

Original languageEnglish (US)
Pages (from-to)519-540
Number of pages22
JournalCirculation research
Issue number4
StatePublished - Feb 17 2023

Bibliographical note

Funding Information:
This project was supported by the National Institutes of Health grants NIAMS R01 AR078571 (R.C.R. Perlingeiro), NIAMS R21 AR079236 (R.C.R. Perlingeiro), NHLBI R01 HL155993 (J.H. van Berlo), NHLBI R01HL160665 (J.H. van Berlo), NHLBI R01 HL137204 (B.M. Ogle), NHLBI R01 HL160779 (B.M. Ogle), and NIAMS R01 AR055685 (M. Kyba). J.H. van Berlo was supported by a Summer’s Wish Pediatric Cardiology Innovators Fund and Regenerative Medicine Minnesota. B.I. Garay was supported by NHLBI F30 HL151138 and NIGMS T32 GM008244. This project also received seed funds from the University of Minnesota Lillehei Heart Institute (R.C.R. Perlingeiro) and the Institute for Engineering in Medicine group grant (B.M. Ogle).

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.


  • cardiac
  • cell division
  • myocytes
  • organoids
  • tissue engineering

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering'. Together they form a unique fingerprint.

Cite this