PUBLICATION

Development of a human cardiac organoid injury model reveals innate regenerative potential

Authors
Voges, H.K., Mills, R.J., Elliott, D.A., Parton, R.G., Porrello, E.R., Hudson, J.E.
ID
ZDB-PUB-170209-9
Date
2017
Source
Development (Cambridge, England)   144(6): 1118-1127 (Journal)
Registered Authors
Parton, Robert G.
Keywords
Cardiac Organoids, Cardiac Tissue Engineering, Injury Model, Regeneration
MeSH Terms
  • Adult
  • Cell Death
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Freezing
  • Heart/embryology*
  • Heart/physiopathology*
  • Heart Function Tests
  • Heart Injuries/pathology
  • Heart Injuries/physiopathology*
  • Humans
  • Hypertrophy
  • Models, Biological*
  • Myocardial Contraction
  • Myocardium/pathology
  • Myocytes, Cardiac/cytology
  • Organoids/embryology*
  • Organoids/ultrastructure
  • Recovery of Function
  • Regeneration*
PubMed
28174241 Full text @ Development
Abstract
The adult human heart possesses a limited regenerative potential following an ischemic event, and undergoes a number of pathological changes in response to injury. While 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 (hCO), which resemble fetal heart tissue and can be used to address this important knowledge gap. This study aimed to characterise the regenerative capacity of immature human heart tissue in response to injury. Following cryoinjury with a dry ice probe, hCO exhibited an endogenous regenerative response with full functional recovery by two weeks following 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 hCO. This study suggests that immature human heart tissue has an intrinsic capacity to regenerate.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping