Journal article
Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-proliferative Compounds Acting via the Mevalonate Pathway
RJ Mills, BL Parker, GA Quaife-Ryan, HK Voges, EJ Needham, A Bornot, M Ding, H Andersson, M Polla, DA Elliott, L Drowley, M Clausen, AT Plowright, IP Barrett, QD Wang, DE James, ER Porrello, JE Hudson
Cell Stem Cell | CELL PRESS | Published : 2019
Abstract
We have previously developed a high-throughput bioengineered human cardiac organoid (hCO) platform, which provides functional contractile tissue with biological properties similar to native heart tissue, including mature, cell-cycle-arrested cardiomyocytes. In this study, we perform functional screening of 105 small molecules with pro-regenerative potential. Our findings reveal surprising discordance between our hCO system and traditional 2D assays. In addition, functional analyses uncovered detrimental effects of many hit compounds. Two pro-proliferative small molecules without detrimental impacts on cardiac function were identified. High-throughput proteomics in hCO revealed synergistic ac..
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Funding Acknowledgements
We used the Australian National Fabrication Facility Queensland Node for the fabrication of the organoid screening platform molds. B.L.P., D.E.J., E.R.P., and J.E.H. are supported by fellowships and project grants from the National Health and Medical Research Council, the National Heart Foundation, Stem Cells Australia, The Royal Children's Hospital Foundation, The University of Queensland., and QIMR Berghofer Medical Research Institute. The Murdoch Children's Research Institute is supported by the Victorian Government's Operational Infrastructure Support Program. The contents of the published material are solely the responsibility of the authors and do not reflect the views of the funding bodies.