scholarly journals Microenvironmental changes by placenta-derived mesenchymal stem cells restore the ovarian function in ovariectomized rat via activated PI3K-FOXO3 pathway

2020 ◽  
Author(s):  
Jong Ho Choi ◽  
Jin Seok ◽  
Seung Mook Lim ◽  
Tae Hee Kim ◽  
Gi Jin Kim

Abstract Background: Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, the mechanistic studies of the function of these cells have been insufficient. As ovarian failures cause anovulation as well as ovarian steroid hormonal unbalances, the specific aims of this study were to analyze the therapeutic role of placenta derived MSCs (PD-MSCs) in an ovarian-failure ovariectomy (OVX) rat model and evaluate whether PD-MSCs transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling. Methods: Blood and ovary tissue were collected and analyzed after various PD-MSCs Tx treatments in the ovariectomized rat model. Changes in the expression of folliculogenesis and ovary regeneration-related genes due to PD-MSCs treatments were analyzed by qRT-PCR, Western blotting, and histological analysis. Results: The levels of hormones related to ovary function were significantly increased in the PD-MSCs Tx groups compared with those of the non-transplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with increased expression of genes related to folliculogenesis for PD-MSCs Tx compared with NTx groups. Furthermore, PD-MSCs Tx induced maturation of follicles by increasing the phosphorylation of GSK3 beta and FOXO3 (p<0.05) and shifting the balance of growth and apoptosis in the oocytes. Conclusions: Taken together, PD-MSCs Tx can restore the ovarian function as well as induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.

2020 ◽  
Author(s):  
Jong Ho Choi ◽  
Jin Seok ◽  
Seung Mook Lim ◽  
Tae Hee Kim ◽  
Gi Jin Kim

Abstract Background: Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, the mechanistic studies of the function of these cells have been insufficient. As ovarian failures cause anovulation as well as ovarian steroid hormonal unbalances, the specific aims of this study were to analyze the therapeutic role of placenta derived MSCs (PD-MSCs) in an ovarian-failure ovariectomy (OVX) rat model and evaluate whether PD-MSCs transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling. Methods: Blood and ovary tissue were collected and analyzed after various PD-MSCs Tx treatments in the ovariectomized rat model. Changes in the expression of folliculogenesis and ovary regeneration-related genes due to PD-MSCs treatments were analyzed by qRT-PCR, Western blotting, and histological analysis. Results: The levels of hormones related to ovary function were significantly increased in the PD-MSCs Tx groups compared with those of the non-transplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with increased expression of genes related to folliculogenesis for PD-MSCs Tx compared with NTx groups. Furthermore, PD-MSCs Tx induced maturation of follicles by increasing the phosphorylation of GSK3 beta and FOXO3 (p<0.05) and shifting the balance of growth and apoptosis in the oocytes. Conclusions: Taken together, PD-MSCs Tx can restore the ovarian function as well as induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.


2020 ◽  
Author(s):  
Jong Ho Choi ◽  
Jin Seok ◽  
Seung Mook Lim ◽  
Tae Hee Kim ◽  
Gi Jin Kim

Abstract Background: Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, mechanistic studies of the function of these cells have been insufficient. As ovarian failure causes anovulation as well as ovarian steroid hormonal imbalances, the specific aims of this study were to analyze the therapeutic role of placenta-derived MSCs (PD-MSCs) in an ovarian failure ovariectomy (OVX) rat model and evaluate whether PD-MSC transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling.Methods: Blood and ovary tissue were collected and analyzed after various PD-MSC Tx treatments in an ovariectomized rat model. Changes in the expression of folliculogenesis- and ovary regeneration-related genes induced by PD-MSC treatments were analyzed by qRT-PCR, Western blotting, and histological analysis.Results: The levels of hormones related to ovary function were significantly increased in the PD-MSC Tx groups compared with those in the nontransplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with increased expression of genes related to folliculogenesis in the PD-MSC Tx groups compared with NTx groups. Furthermore, Tx PD-MSCs induced follicle maturation by increasing the phosphorylation of GSK3 beta and FOXO3 (p<0.05) and shifting the balance of growth and apoptosis in oocytes.Conclusions: Taken together, these results show that PD-MSC Tx can restore ovarian function and induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong Ho Choi ◽  
Jin Seok ◽  
Seung Mook Lim ◽  
Tae Hee Kim ◽  
Gi Jin Kim

Abstract Background Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, mechanistic studies of the function of these cells have been insufficient. As ovarian failure causes anovulation as well as ovarian steroid hormonal imbalances, the specific aims of this study were to analyze the therapeutic role of placenta-derived MSCs (PD-MSCs) in an ovarian failure ovariectomy (OVX) rat model and evaluate whether PD-MSC transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling. Methods Blood and ovary tissue were collected and analyzed after various PD-MSC Tx treatments in an ovariectomized rat model. Changes in the expression of folliculogenesis- and ovary regeneration-related genes induced by PD-MSC treatments were analyzed by qRT-PCR, Western blotting, and histological analysis. Results The levels of hormones related to ovary function were significantly increased in the PD-MSC Tx groups compared with those in the nontransplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with the increased expression of genes related to folliculogenesis in the PD-MSC Tx groups compared with the NTx groups. Furthermore, Tx PD-MSCs induced follicle maturation by increasing the phosphorylation of GSK3 beta and FOXO3 (p < 0.05) and shifting the balance of growth and apoptosis in oocytes. Conclusions Taken together, these results show that PD-MSC Tx can restore ovarian function and induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.


Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 591
Author(s):  
Jin Seok ◽  
Hyeri Park ◽  
Jong Ho Choi ◽  
Ja-Yun Lim ◽  
Kyung Gon Kim ◽  
...  

Oxidative stress is one of the major etiologies of ovarian dysfunction, including premature ovarian failure (POF). Previous reports have demonstrated the therapeutic effects of human placenta-derived mesenchymal stem cells (PD-MSCs) in an ovariectomized rat model (OVX). However, their therapeutic mechanism in oxidative stress has not been reported. Therefore, we investigated to profile the exosome of serum and demonstrate the therapeutic effect of PD-MSCs transplantation for the ovary function. We established an OVX model by ovariectomy and PD-MSCs transplantation was conducted by intravenous injection. Additionally, various factors in the exosome were profiled by LC-MS analysis. As a result, the transplanted PD-MSCs were engrafted into the ovary and the existence of antioxidant factors in the exosome. A decreased expression of oxidative stress markers and increased expression of antioxidant markers were shown in the transplantation (Tx) in comparison to the non-transplantation group (NTx) (* p < 0.05). The apoptosis factors were decreased, and ovary function was improved in Tx in comparison to NTx (* p < 0.05). These results suggest that transplanted PD-MSCs restore the ovarian function in an OVX model via upregulated antioxidant factors. These findings offer new insights for further understanding of stem cell therapy for reproductive systems.


2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat

Abstract Alzheimer's disease (AD) is the most prevalent type of dementia characterized by its progression, neurobehavioral and neuro-pathological characteristics, leading to a diverse neuronal loss. Adipose-derived mesenchymal stem cells (ADMSCs) have previously proved potential role in preventing the pathogenesis of several neurodegenerative disorders, so regarded as a promising new approach for AD regenerative therapy. Taurine was found to enhance stem cell activation and propagation yielding a higher concentration of neural progenitors and stem cells, and aid to lessen the number of activated microglia leading to down-regulated inflammation in vitro. The present study aimed to investigate the possible therapeutic potential of ADMSCs and/or taurine in treating AD rat model. It was planned to include three successive phases; induction, withdrawal, and therapeutic phases. Fifty male Wistar rats were divided into 2 main groups: control (C) group and AD model group. Behavioral changes, as manifested by the T-Maze experiment, had been recorded. β-amyloid levels had been measured in brain homogenate and serum by ELISA. Oxidative stress marker (MDA), and anti-oxidant enzymes activity (SOD, GSH, and CAT) in brain, as well as serum acetylcholine esterase activity were spectrophotometrically determined. Pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl2) gene expression in brain were evaluated using RT-qPCR. The histopathological alterations in brain tissues were also observed. The present study proved the potential therapeutic ability of ADMSCs and/or taurine in alleviating the adverse pathological changes induced by AlCl3 in AD rat model at both physiological and molecular levels.


Author(s):  
Qiaojuan Mei ◽  
Hongbei Mou ◽  
Xuemei Liu ◽  
Wenpei Xiang

With the development of regenerative medicine, stem cells are being considered more frequently for the treatment of reproductive aging. Human umbilical cord mesenchymal stem cells have been reported to improve the reserve function of aging ovaries through their homing and paracrine effects. In this process, paracrine factors secreted by stem cells play an important role in ovarian recovery. Although the transplantation of human umbilical cord mesenchymal stem cells to improve ovarian function has been studied with great success in animal models of reproductive aging, their application in clinical research and therapy is still relatively rare. Therefore, this paper reviews the role of human umbilical cord mesenchymal stem cells in the treatment of reproductive aging and their related mechanisms, and it does so in order to provide a theoretical basis for further research and clinical treatment.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Dan Song ◽  
Yun Zhong ◽  
Chunfeng Qian ◽  
Qinyan Zou ◽  
Jian Ou ◽  
...  

Premature ovarian failure (POF) is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX-) induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL) and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs) in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescencein situhybridization (FISH). The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
R. A. Contreras ◽  
F. E. Figueroa ◽  
F. Djouad ◽  
P. Luz-Crawford

Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studiedin vitroandin vivoin experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.


Sign in / Sign up

Export Citation Format

Share Document