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

被引：91

作者：

Cho, Gun-Sik ^{[1
,2
]}

Lee, Dong I. ^{[1
]}

Tampakakis, Emmanouil ^{[1
,2
]}

Murphy, Sean ^{[1
,2
]}

Andersen, Peter ^{[1
,2
]}

Uosaki, Hideki ^{[1
,2
,8
]}

Chelko, Stephen ^{[1
]}

Chakir, Khalid ^{[1
]}

Hong, Ingie ^{[3
]}

Seo, Kinya ^{[1
]}

Chen, Huei-Sheng Vincent ^{[4
]}

Chen, Xiongwen ^{[5
]}

Basso, Cristina ^{[6
,7
]}

Houser, Steven R. ^{[5
]}

Tomaselli, Gordon F. ^{[1
]}

O'Rourke, Brian ^{[1
]}

Judge, Daniel P. ^{[1
]}

Kass, David A. ^{[1
]}

Kwon, Chulan ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[4] Sanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, La Jolla, CA 92037 USA

[5] Temple Univ, Sch Med, Dept Physiol, Philadelphia, PA 19140 USA

[6] Temple Univ, Sch Med, Dept Cardiovasc Res Ctr, Philadelphia, PA 19140 USA

[7] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy

[8] Jichi Med Univ, Ctr Mol Med, Div Regenerat Med, Shimotsuke, Tochigi 3290498, Japan

来源：

CELL REPORTS | 2017年 / 18卷 / 02期

关键词：

PLURIPOTENT STEM-CELLS; REGENERATIVE MEDICINE; FUNCTIONAL MATURATION; RNA-SEQ; MOUSE; MYOCYTES;

D O I：

10.1016/j.celrep.2016.12.040

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：571 / 582

页数：12

共 48 条

[1] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[2] NA-CA EXCHANGE IS REQUIRED FOR REST-DECAY BUT NOT FOR REST-POTENTIATION OF TWITCHES IN RABBIT AND RAT VENTRICULAR MYOCYTES [J].

BASSANI, RA ;

BERS, DM .

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1994, 26 (10) :1335-1347

[3] Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies [J].

Basso, Cristina ;

Czarnowska, Elzbieta ;

Della Barbera, Mila ;

Bauce, Barbara ;

Beffagna, Giorgia ;

Wlodarska, Elzbieta K. ;

Pilichou, Kaltiopi ;

Ramondo, Angelo ;

Lorenzon, Alessandra ;

Wozniak, Olgierd ;

Corrado, Domenico ;

Datiento, Luciano ;

Danieli, Gian Antonio ;

Valente, Marialuisa ;

Nava, Andrea ;

Thiene, Gaetano ;

Rampazzo, Alessandra .

EUROPEAN HEART JOURNAL, 2006, 27 (15) :1847-1854

[4] Arrhythmogenic right ventricular cardiomyopathy/dysplasia: An update [J].

Calkins H. ;

Marcus F. .

Current Cardiology Reports, 2008, 10 (5) :367-375

[5] Central role for GSK3β in the pathogenesis of arrhythmogenic cardiomyopathy [J].

Chelko, Stephen P. ;

Asimaki, Angeliki ;

Andersen, Peter ;

Bedja, Djahida ;

Amat-Alarcon, Nuria ;

DeMazumder, Deeptankar ;

Jasti, Ravirasmi ;

MacRae, Calum A. ;

Leber, Remo ;

Kleber, Andre G. ;

Saffitz, Jeffrey E. ;

Judge, Daniel P. .

JCI INSIGHT, 2016, 1 (05)

[6] L-type Ca2+ channel density and regulation are altered in failing human ventricular myocytes and recover after support with mechanical assist devices [J].

Chen, XW ;

Piancentino, V ;

Furukawa, S ;

Goldman, B ;

Margulies, KB ;

Houser, SR .

CIRCULATION RESEARCH, 2002, 91 (06) :517-524

[7] Fibronectin mediates mesendodermal cell fate decisions [J].

Cheng, Paul ;

Andersen, Peter ;

Hassel, David ;

Kaynak, Bogac L. ;

Limphong, Pattraranee ;

Juergensen, Lonny ;

Kwon, Chulan ;

Srivastava, Deepak .

DEVELOPMENT, 2013, 140 (12) :2587-2596

[8] Regenerative Medicine for the Heart: Perspectives on Stem-Cell Therapy [J].

Cho, Gun-Sik ;

Fernandez, Laviel ;

Kwon, Chulan .

ANTIOXIDANTS & REDOX SIGNALING, 2014, 21 (14) :2018-2031

[9] Matrigel Mattress A Method for the Generation of Single Contracting Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes [J].

Feaster, Tromondae K. ;

Cadar, Adrian G. ;

Wang, Lili ;

Williams, Charles H. ;

Chun, Young Wook ;

Hempel, Jonathan E. ;

Bloodworth, Nathaniel ;

Merryman, W. David ;

Lim, Chee Chew ;

Wu, Joseph C. ;

Knollmann, Bjoern C. ;

Hong, Charles C. .

CIRCULATION RESEARCH, 2015, 117 (12) :995-+

[10] Use of differentiated pluripotent stem cells in replacement therapy for treating disease [J].

Fox, Ira J. ;

Daley, George Q. ;

Goldman, Steven A. ;

Huard, Johnny ;

Kamp, Timothy J. ;

Trucco, Massimo .

SCIENCE, 2014, 345 (6199) :889-+

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