In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts

We hypothesized that the neonatal rat heart would bring transplanted human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to maturity as it grows to adult size. In neonatal rat heart, engrafted hiPSC derivatives developed partially matured myofibrils after 3 months, with increasing...

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Main Authors: Shin Kadota, Lil Pabon, Hans Reinecke, Charles E. Murry
Format: Article
Language:English
Published: Elsevier 2017-02-01
Series:Stem Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671116302478
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author Shin Kadota
Lil Pabon
Hans Reinecke
Charles E. Murry
author_facet Shin Kadota
Lil Pabon
Hans Reinecke
Charles E. Murry
author_sort Shin Kadota
collection DOAJ
description We hypothesized that the neonatal rat heart would bring transplanted human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to maturity as it grows to adult size. In neonatal rat heart, engrafted hiPSC derivatives developed partially matured myofibrils after 3 months, with increasing cell size and sarcomere length. There was no difference between grafts from hiPSC-CMs or hiPSC-derived cardiac progenitors (hiPSC-CPs) at 3 months, nor was maturation influenced by infarction. Interestingly, the infarcted adult heart induced greater human cardiomyocyte hypertrophy and induction of cardiac troponin I expression than the neonatal heart. Although human cardiomyocytes at all time points were significantly smaller than the host rat cardiomyocytes, transplanted neonatal rat cardiomyocytes reached adult size and structure by 3 months. Thus, the adult rat heart induces faster maturation than the neonatal heart, and human cardiomyocytes mature more slowly than rat cardiomyocytes. The slower maturation of human cardiomyocytes could be related to environmental mismatch or cell-autonomous factors.
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spelling doaj.art-d4f6075a460d4ab68a2943a6c93abd822022-12-22T02:51:26ZengElsevierStem Cell Reports2213-67112017-02-018227828910.1016/j.stemcr.2016.10.009In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat HeartsShin Kadota0Lil Pabon1Hans Reinecke2Charles E. Murry3Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USADepartment of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USADepartment of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USADepartment of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USAWe hypothesized that the neonatal rat heart would bring transplanted human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to maturity as it grows to adult size. In neonatal rat heart, engrafted hiPSC derivatives developed partially matured myofibrils after 3 months, with increasing cell size and sarcomere length. There was no difference between grafts from hiPSC-CMs or hiPSC-derived cardiac progenitors (hiPSC-CPs) at 3 months, nor was maturation influenced by infarction. Interestingly, the infarcted adult heart induced greater human cardiomyocyte hypertrophy and induction of cardiac troponin I expression than the neonatal heart. Although human cardiomyocytes at all time points were significantly smaller than the host rat cardiomyocytes, transplanted neonatal rat cardiomyocytes reached adult size and structure by 3 months. Thus, the adult rat heart induces faster maturation than the neonatal heart, and human cardiomyocytes mature more slowly than rat cardiomyocytes. The slower maturation of human cardiomyocytes could be related to environmental mismatch or cell-autonomous factors.http://www.sciencedirect.com/science/article/pii/S2213671116302478maturationhuman pluripotent stem cell-derived cardiomyocyteneonatal rat
spellingShingle Shin Kadota
Lil Pabon
Hans Reinecke
Charles E. Murry
In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts
Stem Cell Reports
maturation
human pluripotent stem cell-derived cardiomyocyte
neonatal rat
title In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts
title_full In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts
title_fullStr In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts
title_full_unstemmed In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts
title_short In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts
title_sort in vivo maturation of human induced pluripotent stem cell derived cardiomyocytes in neonatal and adult rat hearts
topic maturation
human pluripotent stem cell-derived cardiomyocyte
neonatal rat
url http://www.sciencedirect.com/science/article/pii/S2213671116302478
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