Development of a human cardiac organoid injury model reveals innate regenerative potential.
The adult human heart possesses a limited regenerative potential following an ischemic event, and undergoes a number of pathological changes in response to injury. Although cardiac regeneration has been documented in zebrafish and neonatal mouse hearts, it is currently unknown whether the immature human heart is capable of undergoing complete regeneration. Combined progress in pluripotent stem cell differentiation and tissue engineering has facilitated the development of human cardiac organoids (hCOs), which resemble fetal heart tissue and can be used to address this important knowledge gap. This study aimed to characterize the regenerative capacity of immature human heart tissue in response to injury. Following cryoinjury with a dry ice probe, hCOs exhibited an endogenous regenerative response with full functional recovery 2 weeks after acute injury. Cardiac functional recovery occurred in the absence of pathological fibrosis or cardiomyocyte hypertrophy. Consistent with regenerative organisms and neonatal human hearts, there was a high basal level of cardiomyocyte proliferation, which may be responsible for the regenerative capacity of the hCOs. This study suggests that immature human heart tissue has an intrinsic capacity to regenerate.
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Holly K
HK
Voges
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Richard J
RJ
Mills
Murdoch Children's Research Institute, Royal Children's Hospital, School of Biosciences, The University of Melbourne, Parkville, Victoria 3052, Australia.
David A
DA
Elliott
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.|Centre for Microscopy and Microanalysis, The University of Queensland, St Lucia, Queensland 4072, Australia.
Robert G
RG
Parton
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia e.porrello@uq.edu.au j.hudson@uq.edu.au.
Enzo R
ER
Porrello
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia e.porrello@uq.edu.au j.hudson@uq.edu.au.
James E
0000-0003-0832-9356
JE
Hudson
D000328:Adult; D016923:Cell Death; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D005615:Freezing; D006321:Heart / Q000196:embryology* / Q000503:physiopathology*; D006334:Heart Function Tests; D006335:Heart Injuries / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006984:Hypertrophy; D008954:Models, Biological; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology; D009940:Organoids / Q000196:embryology* / Q000648:ultrastructure; D020127:Recovery of Function; D012038:Regeneration
Cardiac organoids; Cardiac tissue engineering; Injury model; Regeneration