Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy
Author(s) -
Gun-Sik Cho,
Dong I. Lee,
Emmanouil Tampakakis,
Sean Murphy,
Peter Andersen,
Hideki Uosaki,
Stephen P. 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
Publication year - 2017
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2016.12.040
Subject(s) - transplantation , induced pluripotent stem cell , cardiomyopathy , phenotype , pathogenesis , zebrafish , biology , embryonic stem cell , heart transplantation , disease , in vivo , heart disease , fetus , medicine , bioinformatics , microbiology and biotechnology , pathology , immunology , heart failure , genetics , gene , pregnancy
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.
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