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Exosomal miRNAs derived from specific cardiac progenitor cells exert strong therapeutic effect on myocardial infarction
Author(s) -
Xuan Wanling,
Wang Lei,
Tang Yaoliang,
Ashraf Muhammad
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.675.10
Subject(s) - microvesicles , microrna , microbiology and biotechnology , progenitor cell , cardiac function curve , angiogenesis , myocardial infarction , microarray analysis techniques , cancer research , in vitro , function (biology) , chemistry , biology , pharmacology , stem cell , gene expression , medicine , gene , biochemistry , cardiology , heart failure
Objective miRNA signatures are unique in exosomes amongst different parent cells. Here, we isolated and characterized exosomes from small molecule induced cardiac progenitor cells (Exo‐CPC iso ) and determined their effects on cardiac cells in vitro and on mice hearts following myocardial infarction (MI). Methods and results miR‐373, miR‐367, miR‐520 and miR‐548 were significantly overexpressed in Exo‐CPC iso and these miRNA microarray data were confirmed with real‐time PCR. Go enrichment analysis based on miRNA‐targeted genes showed that biological process included organelle, molecular function, response to stress and mitotic cell cycle. Interestingly, expression of fibrotic genes in cultured fibroblasts stimulated with TGF‐β was significantly downregulated after treatment with Exo‐CPC iso . Loss‐of‐function analysis using miR‐373 inhibitor confirmed that enrichment of miR‐373 was the major contributor to reversion of TGF‐β stimulation in fibroblasts. Moreover, intramyocardial injection of Exo‐CPC iso exerted favorable cardioprotective effects on cardiomyocyte proliferation, angiogenesis and preservation of cardiac function in mice one month post‐MI compared with PBS and Exo‐iPSC treated mice. Conclusion Exosomes derived from cardiogenic small molecule induced‐CPCs were highly effective in myocardial repair and functional improvement after MI due to their unique miRNA cargo contents. These data further suggest that cellular source of exosomes has a strong bearing on their therapeutic potential. Support or Funding Information This study was supported by the National Institutes of Health grants, RO1 HL126516, HL134354, 2RHL086555 and RO1 AR070029. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .