BACKGROUND: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. METHODS AND RESULTS: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p<0.05). CONCLUSION: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.
BACKGROUND: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. METHODS AND RESULTS:CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mousemyocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p<0.05). CONCLUSION: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.
Authors: G Hu; H Yao; A D Chaudhuri; M Duan; S V Yelamanchili; H Wen; P D Cheney; H S Fox; S Buch Journal: Cell Death Dis Date: 2012-08-30 Impact factor: 8.469
Authors: Jamie O Brett; Valérie M Renault; Victoria A Rafalski; Ashley E Webb; Anne Brunet Journal: Aging (Albany NY) Date: 2011-02 Impact factor: 5.682
Authors: Masamitsu Kanada; Michael H Bachmann; Jonathan W Hardy; Daniel Omar Frimannson; Laura Bronsart; Andrew Wang; Matthew D Sylvester; Tobi L Schmidt; Roger L Kaspar; Manish J Butte; A C Matin; Christopher H Contag Journal: Proc Natl Acad Sci U S A Date: 2015-02-23 Impact factor: 11.205