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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Veröffentlicht in:	Stem cell reports Jg. 16; H. 3; S. 519 - 533
Hauptverfasser:	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
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Elsevier Inc 09.03.2021 Elsevier
Schlagworte:	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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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. [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.
AbstractList	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. 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. • 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. 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.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. 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.
Author	Londono, Pilar Cleveland, Joseph C. Knight, Walter E. D'Alessandro, Angelo Ambardekar, Amrut V. McKinsey, Timothy A. Jeong, Mark Y. Chatfield, Kathryn C. Song, Kunhua Reisz, Julie A. Bai, Betty Sparagna, Genevieve C. Zhao, Yuanbiao Taylor, Matthew R.G. Bristow, Michael R. Xu, Hongyan Cao, Yingqiong Chi, Congwu Walker, Lori A. Woulfe, Kathleen C. Du, Yanmei Lin, Ying-Hsi Brown, Benjamin C. Buttrick, Peter M.
Author_xml	– sequence: 1 givenname: Walter E. surname: Knight fullname: Knight, Walter E. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 2 givenname: Yingqiong surname: Cao fullname: Cao, Yingqiong organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 3 givenname: Ying-Hsi surname: Lin fullname: Lin, Ying-Hsi organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 4 givenname: Congwu surname: Chi fullname: Chi, Congwu organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 5 givenname: Betty surname: Bai fullname: Bai, Betty organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 6 givenname: Genevieve C. surname: Sparagna fullname: Sparagna, Genevieve C. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 7 givenname: Yuanbiao surname: Zhao fullname: Zhao, Yuanbiao organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 8 givenname: Yanmei surname: Du fullname: Du, Yanmei organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 9 givenname: Pilar surname: Londono fullname: Londono, Pilar organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 10 givenname: Julie A. surname: Reisz fullname: Reisz, Julie A. organization: Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 11 givenname: Benjamin C. surname: Brown fullname: Brown, Benjamin C. organization: Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 12 givenname: Matthew R.G. surname: Taylor fullname: Taylor, Matthew R.G. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 13 givenname: Amrut V. surname: Ambardekar fullname: Ambardekar, Amrut V. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 14 givenname: Joseph C. surname: Cleveland fullname: Cleveland, Joseph C. organization: The Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 15 givenname: Timothy A. surname: McKinsey fullname: McKinsey, Timothy A. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 16 givenname: Mark Y. surname: Jeong fullname: Jeong, Mark Y. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 17 givenname: Lori A. surname: Walker fullname: Walker, Lori A. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 18 givenname: Kathleen C. surname: Woulfe fullname: Woulfe, Kathleen C. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 19 givenname: Angelo surname: D'Alessandro fullname: D'Alessandro, Angelo organization: Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 20 givenname: Kathryn C. surname: Chatfield fullname: Chatfield, Kathryn C. organization: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 21 givenname: Hongyan surname: Xu fullname: Xu, Hongyan organization: Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA – sequence: 22 givenname: Michael R. surname: Bristow fullname: Bristow, Michael R. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 23 givenname: Peter M. surname: Buttrick fullname: Buttrick, Peter M. organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA – sequence: 24 givenname: Kunhua surname: Song fullname: Song, Kunhua email: kunhua.song@cuanschutz.edu organization: Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Keywords	hiPSC-CM maturation hypertrophic cardiomyopathy cardiomyocyte maturation hiPSC-CM HIF1α disease modeling
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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
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Snippet	Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a...
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SubjectTerms	cardiomyocyte maturation disease modeling HIF1α hiPSC-CM hiPSC-CM maturation hypertrophic cardiomyopathy
Title	Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy
URI	https://dx.doi.org/10.1016/j.stemcr.2021.01.018 https://www.ncbi.nlm.nih.gov/pubmed/33636116 https://www.proquest.com/docview/2494304439 https://pubmed.ncbi.nlm.nih.gov/PMC7940251
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