Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.
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.
Institute of Medical Biology, ASTAR, 138648 Singapore.
Ruenn Chai
RC
Lai
Fatih
F
Arslan
May May
MM
Lee
Newman Siu Kwan
NS
Sze
Andre
A
Choo
Tian Sheng
TS
Chen
Manuel
M
Salto-Tellez
Leo
L
Timmers
Chuen Neng
CN
Lee
Reida Menshawe
RM
El Oakley
Gerard
G
Pasterkamp
Dominique P V
DP
de Kleijn
Sai Kiang
SK
Lim
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000628:therapy*; D015427:Reperfusion Injury / Q000628:therapy*; D060225:Tetraspanin 28; D060245:Tetraspanin 29
D015703:Antigens, CD; C554798:CD81 protein, human; C554869:CD9 protein, human; D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; C554799:Cd81 protein, mouse; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; C492144:Pdcd6ip protein, mouse; D060225:Tetraspanin 28; D060245:Tetraspanin 29