Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy

Walter E. Knight; Yingqiong Cao; Ying Hsi Lin; Congwu Chi; Betty Bai; Genevieve C. Sparagna; Yuanbiao Zhao; Yanmei Du; Pilar Londono; Julie A. Reisz; Benjamin C. Brown; Matthew R.G. Taylor; Amrut V. Ambardekar; Joseph C. Cleveland; Timothy A. McKinsey; Mark Y. Jeong; Lori A. Walker; Kathleen C. Woulfe; Angelo D'Alessandro; Kathryn C. Chatfield; Hongyan Xu; Michael R. Bristow; Peter M. Buttrick; Kunhua Song

doi:10.1016/j.stemcr.2021.01.018

Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy

Walter E. Knight, Yingqiong Cao, Ying Hsi Lin, Congwu Chi, Betty Bai, Genevieve C. Sparagna, Yuanbiao Zhao, Yanmei Du, Pilar Londono, Julie A. Reisz, Benjamin C. Brown, Matthew R.G. Taylor, Amrut V. Ambardekar, Joseph C. Cleveland, Timothy A. McKinsey, Mark Y. Jeong, Lori A. Walker, Kathleen C. Woulfe, Angelo D'Alessandro, Kathryn C. ChatfieldHongyan Xu, Michael R. Bristow, Peter M. Buttrick, Kunhua Song

Biostats & Data Science

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Here, we sought to develop a simple method that could drive cultured hiPSC-CMs toward maturity across a number of phenotypes, with the aim of utilizing mature hiPSC-CMs to model human cardiovascular disease. hiPSC-CMs were cultured in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics of adult human cardiomyocytes, including elongated cell morphology, sarcomeric maturity, and increased myofibril contractile force. In addition, mature hiPSC-CMs develop pathological hypertrophy, with associated myofibril relaxation defects, in response to either a pro-hypertrophic agent or genetic mutations. The more mature hiPSC-CMs produced by these methods could serve as a useful in vitro platform for characterizing cardiovascular disease.

Original language	English (US)
Pages (from-to)	519-533
Number of pages	15
Journal	Stem Cell Reports
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2021.01.018
State	Published - Mar 9 2021

Keywords

HIF1α
cardiomyocyte maturation
disease modeling
hiPSC-CM
hiPSC-CM maturation
hypertrophic cardiomyopathy

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.stemcr.2021.01.018

Cite this

Knight, W. E., Cao, Y., Lin, Y. H., Chi, C., Bai, B., Sparagna, G. C., Zhao, Y., Du, Y., Londono, P., Reisz, J. A., Brown, B. C., Taylor, M. R. G., Ambardekar, A. V., Cleveland, J. C., McKinsey, T. A., Jeong, M. Y., Walker, L. A., Woulfe, K. C., D'Alessandro, A., ... Song, K. (2021). Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy. Stem Cell Reports, 16(3), 519-533. https://doi.org/10.1016/j.stemcr.2021.01.018

Knight, WE, Cao, Y, Lin, YH, Chi, C, Bai, B, Sparagna, GC, Zhao, Y, Du, Y, Londono, P, Reisz, JA, Brown, BC, Taylor, MRG, Ambardekar, AV, Cleveland, JC, McKinsey, TA, Jeong, MY, Walker, LA, Woulfe, KC, D'Alessandro, A, Chatfield, KC, Xu, H, Bristow, MR, Buttrick, PM & Song, K 2021, 'Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy', Stem Cell Reports, vol. 16, no. 3, pp. 519-533. https://doi.org/10.1016/j.stemcr.2021.01.018

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abstract = "Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Here, we sought to develop a simple method that could drive cultured hiPSC-CMs toward maturity across a number of phenotypes, with the aim of utilizing mature hiPSC-CMs to model human cardiovascular disease. hiPSC-CMs were cultured in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics of adult human cardiomyocytes, including elongated cell morphology, sarcomeric maturity, and increased myofibril contractile force. In addition, mature hiPSC-CMs develop pathological hypertrophy, with associated myofibril relaxation defects, in response to either a pro-hypertrophic agent or genetic mutations. The more mature hiPSC-CMs produced by these methods could serve as a useful in vitro platform for characterizing cardiovascular disease.",

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AU - Bai, Betty

AU - Sparagna, Genevieve C.

AU - Zhao, Yuanbiao

AU - Du, Yanmei

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AU - Woulfe, Kathleen C.

AU - D'Alessandro, Angelo

AU - Chatfield, Kathryn C.

AU - Xu, Hongyan

AU - Bristow, Michael R.

AU - Buttrick, Peter M.

AU - Song, Kunhua

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Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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