Background
Human amnion-derived mesenchymal stem cells (hAD-MSCs) have the features of mesenchymal stem cells (MSCs). Low-intensity pulsed ultrasound (LIPUS) can promote the expression of various growth factors and anti-inflammatory molecules that are necessary to keep the follicle growing and to reduce granulosa cell (GC) apoptosis in the ovary. This study aims to explore the effects of LIPUS-pretreated hAD-MSC transplantation on chemotherapy-induced primary ovarian insufficiency (POI) in rats.
Conclusion
Both hAD-MSC transplantation and LIPUS-pretreated hAD-MSC transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. LIPUS-pretreated hAD-MSC transplantation is more advantageous for reducing inflammation, improving the local microenvironment, and inhibiting GC apoptosis induced by chemotherapy in ovarian tissue of POI rats.
Methods
The animals were divided into control, POI, hAD-MSC treatment, and LIPUS-pretreated hAD-MSC treatment groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX). The hAD-MSCs isolated from the amnion were exposed to LIPUS or sham irradiation for 5 consecutive days and injected into the tail vein of POI rats. Expression and secretion of growth factors promoted by LIPUS in hAD-MSCs were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) in vitro. Estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, GC apoptosis, Bcl2 and Bax expression, and pro-inflammatory cytokine levels in ovaries were examined.
Results
Primary hAD-MSCs were successfully isolated from the amnion. LIPUS promoted the expression and secretion of growth factors in hAD-MSCs in vitro. Both hAD-MSC and LIPUS-pretreated hAD-MSC transplantation increased the body and reproductive organ weights, improved ovarian function, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs increased the Bcl-2/Bax ratio and reduced GC apoptosis and ovarian inflammation induced by chemotherapy in ovaries. These effects could be improved by pretreatment with LIPUS on hAD-MSCs.