| BACKGROUND AND AIM Stem cell therapy has already come a long way to regenerate damaged hearts but the low survival rate of transplanted cells limits their therapeutic efficacy.Recently,exosomesare proposed to regulate multiple cellular processes via mediating cell survival and communication among cells.Rab27 a,a member of Rab family of small GTPases,plays a critical role in secretion of exosomes.The current study aims to investigate whether injured cardiomyocytesderived exosomes(cardiac exosomes)affect the survival of transplanted bone marrow mesenchymal stem cells(BMSCs)in infarcted heart.METHODS To mimic the harsh microenvironment in infarcted heart that the cardiomyocytes(CMs)or transplanted BMSCs encountered in vivo,cardiomyocytes conditioned medium and cardiac exosomes collected from H2O2-treated cardiomyocytes culture medium were cultured with BMSCs under oxidative stress in vitro.In order to explore the role of cardiac exosomes in the survival of transplanted BMSCs in vivo,we constructed Rab27 a knockout(KO)mice model by a TALEN(transcription activator-like effector nuclease)genome-editing technique.Male mouse GFP-modified BMSCs were implanted into the viable myocardium bordering the infarction in Rab27 a KO and wild type female mice.RESULTS In vitro,cardiomyocytes conditioned medium and cardiac exosomes significantly accelerated the injuries of BMSCs induced by H2O2,as indicated by theincreased cleavedcaspase-3/caspase-3 and apoptotic percentage,and the decreased ratio of Bcl-2/Bax and cell viability.In vivo,the results showed that the transplanted BMSCs survival in infarcted heart was increased in Rab27 a KO mice by the higher level of Y-chromosome Sry DNA,GFP m RNA and the GFP fluorescence signal intensity.CONCLUSION 1 Cardiomyocytes conditioned medium acceleratedapoptosis of BMSCs under oxidative stress.2 Theexosomes in oxidative stressed CMs conditioned mediumhad an important role in promoting H2O2-induced BMSCs apoptosis.3 The injured cardiomyocytes-derivedexosomes accelerated transplanted BMSCs injury in infarcted heart and highlighting a new mechanism of affecting the survival of transplanted cells after myocardial infarction. |
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