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

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...

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Vydáno v:Stem cell reports Ročník 16; číslo 3; s. 519 - 533
Hlavní autoři: Knight, Walter E., Cao, Yingqiong, Lin, Ying-Hsi, Chi, Congwu, Bai, Betty, Sparagna, Genevieve C., Zhao, Yuanbiao, Du, Yanmei, Londono, Pilar, Reisz, Julie A., Brown, Benjamin C., Taylor, Matthew R.G., Ambardekar, Amrut V., Cleveland, Joseph C., McKinsey, Timothy A., Jeong, Mark Y., Walker, Lori A., Woulfe, Kathleen C., D'Alessandro, Angelo, Chatfield, Kathryn C., Xu, Hongyan, Bristow, Michael R., Buttrick, Peter M., Song, Kunhua
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 09.03.2021
Elsevier
Témata:
cardiomyocyte maturation
disease modeling
HIF1α
hiPSC-CM
hiPSC-CM maturation
hypertrophic cardiomyopathy
hiPSC-CM maturation
hypertrophic cardiomyopathy
cardiomyocyte maturation
hiPSC-CM
HIF1α
disease modeling
ISSN:2213-6711, 2213-6711
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Shrnutí: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. [Display omitted] •Standard (glucose) cultured hiPSC-CMs demonstrate a blunted hypertrophic response•A maturation method induces hiPSC-CM maturation and suppresses HIF1A expression•Mature hiPSC-CMs demonstrate improved sarcomeric morphology and contractility•Mature hiPSC-CMs respond to agonist- or mutation-induced hypertrophy In this article, Song and colleagues show that a combination of fatty acid medium and micropatterned surfaces induces maturation in human induced pluripotent stem cell-derived cardiomyocytes. Matured cells display improved sarcomere morphology, metabolic maturation, and contractility. These cells also show increased sensitivity to hypertrophic stimuli, including hypertrophic agonist and genetic mutations, representing an ideal system to model cardiovascular disease.
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Present address: Duke-NUS Medical School, Singapore 169609, Singapore
Present address: Cornell University, Ithaca, NY 14850, USA
Present address: Kaiser Permanente, Denver, CO 80205, USA
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2021.01.018