Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb
Fibroin
Exosome
DOI:
10.1016/j.msec.2019.01.122
Publication Date:
2019-01-28T10:09:51Z
AUTHORS (14)
ABSTRACT
Vascular disease is a major complication of aging, but the molecular mechanisms underlying aging-induced vascular dysfunction remain unclear, and there no effective treatment to prevent aging induced diseases. The objectives present study are identify signaling pathway mediating develop an exosome based therapy inhibit process. We used 11-month-old C57BL6 mice as pre-aging animal model H2O2 treated H9C2 cells in vitro examine therapeutic effect miR-675. found decreased expression potential modulator miR-675 muscle, upregulated marker β-gal TGF-β1. also that mimic staining cells. Dual-luciferase reporter assays verified TGF-β1 target gene Moreover, senescent incubated with exosomes isolated from UMSCs transfected showed increased miR-675, reduced activity protein levels employed silk fibroin hydrogel encapsulate order prolong half-life vivo. Fourier transform infrared spectroscopy (FTIR) revealed were successfully encapsulated by hydrogel. Laser Doppler perfusion imaging promote blood ischemic hindlimbs. demonstrated provided sustained release vitro, retention time red fluorescent PKH26-exosome tissue. Taken together, this identified important regulator cell senescence novel strategy deliver powerful treat dysfunction.
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