LAUSR

Human adipose-derived stem cells (hADSCs) offer potential as a therapeutic option for clinical applications because of their cytokine production and capacity for trilineage differentiation. Although the importance of hADSCs in ameliorating the structure and function of injured tissues has been reported, to date few researchers have investigated the effects of hADSCs on natural ovarian aging (NOA). To address the ability of reactivating ovary of natural aging, a NOA mice model and a multitude of human ovarian granule cells (hGCs) that derived from NOA people were prepared to assess the therapy effects and illuminate the mechanism of hADSCs in curing NOA. Our results showed that hADSCs displayed the therapeutic activity on ovarian function (follicle numbers and hormone level) in NOA mice model, promoted the proliferation rate and marker expression of hGCs. Furthermore, yield of hADSCs-secreted HGF and bFGF were higher than other growth factors. Flow cytometry (FACS) showed that growth factor combination (HGF and bFGF) promoted the proliferation and inhibited the apoptosis in hGCs more powerful than using them singly. FACS and ELISA revealed two growth factors inhibited oxidative stress more forceful than one growth factor in vivo and in vitro study. Meantime, protein assay demonstrated that growth factor combination suppress oxidative stress through up-regulating the expression of SIRT1 and FOXO1. These findings, for the first time, demonstrate the molecular cascade and related cell biology events involved in HGF and bFGF derived from hADSCs-improved the ovarian function of natural aging through restraining oxidative stress by activating SIRT1/FOXO1 signaling pathway.