Pretreatment of Cardiac Stem Cells With Exosomes Derived From Mesenchymal Stem Cells Enhances Myocardial Repair

J Am Heart Assoc. 2016 Jan 25;5(1):e002856. doi: 10.1161/JAHA.115.002856.

Abstract

Background: Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model.

Methods and results: DiI-labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose-dependent manner. In a rat myocardial infarction model, MSC exosome-preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long-term cardiac function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in CSCs after MSC exosome treatment.

Conclusions: Pretreatment of CSCs with MSC exosomes provided a promising strategy to improve survival and angiogenic potency of CSCs.

Keywords: angiogenesis; cardiac stem cells; exosomes; miRNA profiling; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / transplantation*
  • Exosomes / metabolism*
  • Fibrosis
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Myocytes, Cardiac / transplantation*
  • Neovascularization, Physiologic*
  • Phenotype
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Regeneration*
  • Signal Transduction
  • Stem Cell Transplantation / methods*
  • Stroke Volume
  • Time Factors
  • Ventricular Function, Left

Substances

  • MicroRNAs