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

Gun-Sik Cho; Dong I. 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

Cell Reports (Jan 2017)

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

Gun-Sik Cho,
Dong I. 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

Affiliations

Gun-Sik Cho: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Dong I. Lee: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Emmanouil Tampakakis: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Sean Murphy: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Peter Andersen: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hideki Uosaki: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Stephen Chelko: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Khalid Chakir: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Ingie Hong: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Kinya Seo: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Huei-Sheng Vincent Chen: Del E. Webb Neuroscience, Aging & Stem Cell Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA
Xiongwen Chen: Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA
Cristina Basso: Department of Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140 USA; Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padova, Italy
Steven R. Houser: Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA
Gordon F. Tomaselli: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Brian O’Rourke: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Daniel P. Judge: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
David A. Kass: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
Chulan Kwon: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author

Journal volume & issue: Vol. 18, no. 2
pp. 571 – 582

Abstract

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Summary: 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. : Pluripotent stem cell (PSC)-derived cells remain fetal like, and this has become a major impediment to modeling adult diseases. Cho et al. find that PSC-derived cardiomyocytes mature into adult cardiomyocytes when transplanted into neonatal rat hearts. This method can serve as a tool to understand maturation and pathogenesis in human cardiomyocytes. Keywords: cardiomyocyte, maturation, iPS, cardiac progenitor, neonatal, disease modeling, cardiomyopathy, ARVC, T-tubule, calcium transient, sarcomere shortening

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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