title: In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts.
abstract: 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.
authors.affiliation: Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Kadota
authors.affiliation: Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Lil
authors.initials: L
authors.lastname: Pabon
authors.affiliation: Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.affiliation: Department of Pathology, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98109, USA. Electronic address: murry@uw.edu.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D033581:Stem Cell Transplantation; D013997:Time Factors
keywords: human pluripotent stem cell-derived cardiomyocyte; maturation; neonatal rat