Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction

Nat Commun. 2019 Jul 16;10(1):3123. doi: 10.1038/s41467-019-11091-2.

Abstract

Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Disease Models, Animal
  • Heart / physiology*
  • Humans
  • Induced Pluripotent Stem Cells / physiology
  • Injections, Intralesional
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Myocardial Infarction / etiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardium / cytology
  • Myocardium / pathology
  • Myocytes, Cardiac / physiology
  • Myocytes, Cardiac / transplantation*
  • Rats
  • Rats, Inbred F344
  • Regeneration*
  • Treatment Outcome