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Stem Cell Res Ther. 2017 Dec 19;8(1):283. doi: 10.1186/s13287-017-0739-3.

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

Author information

1
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, No. 76, Linjiang Road, Chongqing, 400010, China.
2
State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400010, China.
3
Department of Histology and Embryology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, 400010, China.
4
Department of Obstetrics and Gynecology, the Third Affiliated Hospital, Zunyi Medical College, Zunyi, 563000, Guizhou, China.
5
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, No. 76, Linjiang Road, Chongqing, 400010, China. xza20170407@163.com.

Abstract

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.

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.

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.

KEYWORDS:

Chemotherapy; Growth factors; Human amnion-derived mesenchymal stem cells (hAD-MSCs); Low-intensity pulsed ultrasound (LIPUS); Primary ovarian insufficiency/failure (POI/POF)

PMID:
29258619
PMCID:
PMC5735876
DOI:
10.1186/s13287-017-0739-3
[Indexed for MEDLINE]
Free PMC Article

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