Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells

Shunsuke Funakoshi, Ian Fernandes, Olya Mastikhina, Dan Wilkinson, Thinh Tran, Wahiba Dhahri, Amine Mazine, Donghe Yang, Benjamin Burnett, Jeehoon Lee, Stephanie Protze, Gary D. Bader, Sara S. Nunes, Michael Laflamme and Gordon Keller ()
Additional contact information
Shunsuke Funakoshi: University Health Network
Ian Fernandes: University Health Network
Olya Mastikhina: University Health Network
Dan Wilkinson: BlueRock Therapeutics
Thinh Tran: University of Toronto
Wahiba Dhahri: University Health Network
Amine Mazine: University Health Network
Donghe Yang: University Health Network
Benjamin Burnett: BlueRock Therapeutics
Jeehoon Lee: BlueRock Therapeutics
Stephanie Protze: University Health Network
Gary D. Bader: University of Toronto
Sara S. Nunes: University Health Network
Michael Laflamme: University Health Network
Gordon Keller: University Health Network

Nature Communications, 2021, vol. 12, issue 1, 1-23

Abstract: Abstract Compact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23329-z

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DOI: 10.1038/s41467-021-23329-z

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