Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest

• DOI: 10.1073/pnas.1707316114
• Publication Date: 2017-09-16T01:20:20Z
• Authors: Richard J. Mills; Drew M. Titmarsh; Xaver Koenig; Benjamin L. Parker; James G. Ryall; Gregory A. Quaife...; Holly K. Voges; Mark P. Hodson; Charles Ferguson; Lauren Drowley; Alleyn T. Plowright; Elise J. Needham; Qing-Dong Wang; Paul Gregorevic; Mei Xin; Walter G. Thomas; Robert G. Parton; Lars K. Nielsen; Bradley S. Launik...; David E. James; David A. Elliott; Enzo R. Porrello; James E. Hudson
• Keywords: Organoid; Regenerative Medicine; Cardiac muscle; Mammalian heart; Cardiac cell

Significance Engineered cardiac muscle can be used to promote the structural and functional maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). However, previous studies have not yet produced tissues with metabolic proliferative maturation. Here, we develop a 96-well screening platform screen for conditions in engineered muscle. We found that simulating postnatal switch substrates from carbohydrates fatty acids promoted metabolism, DNA damage response, cell cycle arrest hPSC-CM. Our study shows this mechanism harnessed enhance hPSC-CM tissues, which has major implications sciences, drug discovery, regenerative medicine.