Abstract
BackgroundHuman 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.MethodsThe 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.ResultsPrimary 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.ConclusionBoth 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.
Highlights
Human amnion-derived mesenchymal stem cells have the features of mesenchymal stem cells (MSCs)
Our results further showed that, both Human amnion-derived mesenchymal stem cell (hAD-MSC) and Low-intensity pulsed ultrasound (LIPUS)-pretreated hAD-MSCs could reduce inflammation, improve local microenvironment, and inhibit granulosa cell (GC) apoptosis induced by chemotherapy in ovarian tissue, the efficacy of LIPUS-pretreated human amnion-derived mesenchymal stem cells (hADMSCs) were superior to hAD-MSCs
Our studies found that hAD-MSC or LIPUS-pretreated hAD-MSC transplantation downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-6, and Tumor necrosis factor (TNF)-α), which attenuated ovarian inflammation induced by CTX, upregulated vascular endothelial growth factor (VEGF), and reduced the ovarian GC apoptosis in the ovaries of primary ovarian insufficiency (POI) rats
Summary
Human amnion-derived mesenchymal stem cells (hAD-MSCs) have the features of mesenchymal stem cells (MSCs). This study aims to explore the effects of LIPUS-pretreated hAD-MSC transplantation on chemotherapy-induced primary ovarian insufficiency (POI) in rats. Chemotherapy is a commonly used treatment method for women bearing tumors, which could induce ovarian failure, including follicle loss, vascular damage, and tissue fibrosis, especially in young females [4,5,6,7]. Regenerative medicine research suggests that mesenchymal stem cell (MSC) transplantation may restore the ovarian structure and function in animal models of POI, providing an effective treatment method [8, 9]. Human amnion-derived mesenchymal stem cells (hADMSCs) have been shown to have the features of MSCs [10,11,12]. Whether hAD-MSC transplantation can restore the ovarian function in chemotherapy-induced POI is still unknown
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