Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury

Stem Cell Res. 2010 May;4(3):214-22. doi: 10.1016/j.scr.2009.12.003. Epub 2010 Jan 4.

Abstract

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50-100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix. These particles were purified as a homogeneous population of particles with a hydrodynamic radius of 55-65 nm by size-exclusion fractionation on a HPLC. Together these observations indicated that these particles are exosomes. These purified exosomes reduced infarct size in a mouse model of myocardial ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective paracrine effect by secreting exosomes. This novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Calcium-Binding Proteins / metabolism
  • Cardiotonic Agents / therapeutic use
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Exosomes / metabolism*
  • Exosomes / physiology
  • Humans
  • Membrane Glycoproteins / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Microscopy, Electron
  • Myocardial Ischemia / therapy*
  • Reperfusion Injury / therapy*
  • Tetraspanin 28
  • Tetraspanin 29

Substances

  • Antigens, CD
  • CD81 protein, human
  • CD9 protein, human
  • Calcium-Binding Proteins
  • Cardiotonic Agents
  • Cd81 protein, mouse
  • Cd9 protein, mouse
  • Membrane Glycoproteins
  • Pdcd6ip protein, mouse
  • Tetraspanin 28
  • Tetraspanin 29