HGF-modified human umbilical cord mesenchymal stem cells rescue impaired ovarian reserve function in chemotherapy-induced POI rats by improving angiogenesis while decreasing apoptosis and fibrosis in the ovary

Abstract

Complications caused by Primary ovarian insufficiency (POI), including infertility, osteoporosis, cardiovascular diseases and depression, severely affect the life quality of female patients. Although hormone replacement therapy (HRT) can alleviate some long-term complications, there is still no standard treatment for the restoration of ovarian reserve function. Currently, human umbilical cord mesenchymal stem cells (HUCMSC) transplantation showed considerable treatment effect for POI in both rat model and clinic. To improve the effectiveness of naïve HUCMSC (HUCMSC-Null) treatments on POI, an exogenous gene hepatocyte growth factor (HGF) which promotes follicular angiogenesis in POI ovaries was used to modify HUCMSC. Subsequently, HGF-overexpressed HUCMSC (HUCMSC-HGF) was transplanted into the ovaries of chemotherapy-induced POI Sprague-Dawley (SD) rats to observe the effectiveness on POI improvement and its related mechanisms. Our results showed that when compared with POI and HUCMSC-Null treatment group, HUCMSC-HGF significantly improved ovarian reserve function in POI group, which might be attributed to the decrease of ovarian tissue fibrosis and granulosa cells (GCs) apoptosis, and the increase of ovarian angiogenesis mediated by HGF over-expression. The findings suggest that HGF-modified HUCMSC may present a more superior capacity than HUCMSC alone for the rescue of ovarian reserve function in POI.