Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

J Cardiovasc Transl Res. 2018 Oct;11(5):429-437. doi: 10.1007/s12265-018-9824-y. Epub 2018 Oct 1.

Abstract

We demonstrated the effects of exosomes secreted by cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion injury. To investigate the effect of exosomes from C-MSC on angiogenesis, we injected C-MSC-Exo or PBS intramuscularly into ischemic hind limb. Blood perfusion of limb was evaluated by laser Doppler Imaging. We observed that ischemic limb treated with C-MSC-Exo exhibits improved blood perfusion compared to ischemic limb treated with PBS at 2 weeks and 1 month after induction of limb ischemia. To explore the potential mechanisms underlying C-MSC-Exo's angiogenetic effect, we performed microRNA array analysis and identify mmu-miR-7116-5p as the most abundant enriched miRNA detected in C-MSC-Exo. Bioinformatics' analysis shows that miR-7116-5p negatively regulates protein polyubiquitination. In conclusion, our study demonstrated that intramuscular delivery of C-MSC-Exo after limb ischemia improves blood perfusion, and we identified the most abundant miRNAs that are preferentially enriched in C-MSC-Exo.

Keywords: Angiogenesis; Cardiac mesenchymal stem cells; Exosomes; Hind limb ischemia; miR-7116-5p.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity
  • Disease Models, Animal
  • Exosomes / metabolism
  • Exosomes / transplantation*
  • Hindlimb
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / physiopathology
  • Ischemia / surgery*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells* / metabolism
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Muscle, Skeletal / blood supply*
  • Myocardium / cytology*
  • Neovascularization, Physiologic*
  • Phenotype
  • Polyubiquitin / metabolism
  • Regional Blood Flow
  • Stem Cell Transplantation
  • Ubiquitinated Proteins / metabolism
  • Ubiquitination

Substances

  • MicroRNAs
  • Ubiquitinated Proteins
  • Polyubiquitin