Vascular cells improve functionality of human cardiac organoids

Holly K. Voges, Simon Foster, Liam T. Reynolds, Benjamin L Parker, Lynn Devilee, Gregory A. Quaife-Ryan, Patrick R.J. Fortuna, Ellen Mathieson, Rebecca Fitzsimmons, Mary Lor, Christopher Batho, Janice Reid, Mark Pocock, Clayton E. Friedmand, Dalia Mizikovsky, Mathias Francois, Nathan J. Palpant, Elise J. Needham, Marina Peralta, Gonzalo del Monte NietoLynelle K. Jones, Ian M. Smyth, Neda R. Mehdiabadi, Francesca Bolk, Vaibhao Janbandhu, Ernestene Yao, Richard P. Harvey, James J.H. Chong, David A. Elliott, Edouard G. Stanley, Sophie Wiszniak, Quenten Schwarz, David E. James, Richard J. Mills, Enzo R. Porrello, James E. Hudson

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)


Crosstalk between cardiac cells is critical for heart performance. Here we show that vascular cells within human cardiac organoids (hCOs) enhance their maturation, force of contraction, and utility in disease modeling. Herein we optimize our protocol to generate vascular populations in addition to epicardial, fibroblast, and cardiomyocyte cells that self-organize into in-vivo-like structures in hCOs. We identify mechanisms of communication between endothelial cells, pericytes, fibroblasts, and cardiomyocytes that ultimately contribute to cardiac organoid maturation. In particular, (1) endothelial-derived LAMA5 regulates expression of mature sarcomeric proteins and contractility, and (2) paracrine platelet-derived growth factor receptor β (PDGFRβ) signaling from vascular cells upregulates matrix deposition to augment hCO contractile force. Finally, we demonstrate that vascular cells determine the magnitude of diastolic dysfunction caused by inflammatory factors and identify a paracrine role of endothelin driving dysfunction. Together this study highlights the importance and role of vascular cells in organoid models.

Original languageEnglish
Article number112322
Number of pages22
JournalCell Reports
Issue number5
Publication statusPublished - 30 May 2023


  • cardiac organoid
  • CP: Stem cell research
  • disease modeling
  • endothelial cells
  • endothelin-1
  • extracellular matrix
  • inflammation
  • LAMA5
  • PDGF

Cite this