Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

Gun Sik Cho, Dong Lee, Emmanouil Tampakakis, Sean Murphy, Peter Andersen, Hideki Uosaki, Stephen Chelko, Khalid Chakir, Ingie Hong, Kinya Seo, Huei Sheng Vincent Chen, Xiongwen Chen, Cristina Basso, Steven R. Houser, Gordon F. Tomaselli, Brian O'Rourke, Daniel P. Judge, David A Kass, Chulan Kwon

Research output: Contribution to journalArticle

Abstract

Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalCell Reports
Volume18
Issue number2
DOIs
Publication statusPublished - Jan 10 2017

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Keywords

  • ARVC
  • calcium transient
  • cardiac progenitor
  • cardiomyocyte
  • cardiomyopathy
  • disease modeling
  • iPS
  • maturation
  • neonatal
  • sarcomere shortening
  • T-tubule

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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