Effects of low-intensity pulsed ultrasound (LIPUS)-pretreated human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation on primary ovarian insufficiency in rats

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.

Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review

“…Scientists recently reported that stem cell transplantation improves ovarian function by increasing the expression of related hormones and by preventing GC apoptosis, which suggests a therapeutic potential [30]. As shown in Table 1, the therapeutic effects of stem cells can be measured by several factors, such as folliculogenesis, the GC apoptosis rate, vascular formation, the pregnancy rate and the regulation of hormone levels (Table 1) [42].…”

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…Indeed, in a study using low-intensity pulsed ultrasound (LIPUS)-pretreated AD-MSCs, the expression of several growth factors, including IGF1, FGF2, and VEGF, reduced the expression of IL-1β, IL-6, and TNF-α in the ovaries of POF rats. Interestingly, LIPUS pretreatment with AD-MSC transplantation was more effective in decreasing chemotherap yinduced inflammation and apoptosis in the ovarian tissue of POF rats(122). Another study examined the levels of monocyte chemotactic protein-1 (MCP-1), one of the key chemokines in normal and preeclamptic pregnancies, but observed no significant difference in its expression in AD-MSCs(123).…”

Low-intensity ultrasound combined with allogenic adipose-derived mesenchymal stem cells (AdMSCs) in radiation-induced skin injury treatment

“…In the combined treatment, the effects of ultrasound on cells before and after the transplantation of AdMSCs at the cavitation threshold mechanical index of the culture medium and skin tissue were studied for delaying and preventing radiation damage. In a similar study, Ling et al 12 investigated the effect of ultrasound radiation at a frequency of 0.25 MHz and an intensity of 30 mW/cm 2 on AdMSCs before transplantation. After 5 days of ultrasonic irradiation for 30 min, the cells were injected through the tail vein of a mouse which had ovarian failure due to chemotherapy.…”

“…Low-intensity ultrasound is a special type of energy that results in the transmission of acoustic pressure and mechanical stress. The main idea behind the use of low-intensity ultrasound in the medical field is the reconstruction of radiation injuries as a non-ionization method 12 .…”