scholarly journals Placenta-Derived Mesenchymal Stem Cells Restore the Ovary Function in an Ovariectomized Rat Model via an Antioxidant Effect

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 591
Author(s):  
Jin Seok ◽  
Hyeri Park ◽  
Jong Ho Choi ◽  
Ja-Yun Lim ◽  
Kyung Gon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Ovarian Function ◽  
Ovariectomized Rat ◽  
Therapeutic Effects ◽  
Ovary Function ◽  
Effect Of Pd ◽  
Antioxidant Markers

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.

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
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Ovarian Function ◽  
Therapeutic Potential ◽  
Ovariectomized Rat ◽  
Expression Of Genes ◽  
Ovarian Folliculogenesis ◽  
Ovary Function

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.

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
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Ovarian Function ◽  
Therapeutic Potential ◽  
Ovariectomized Rat ◽  
Expression Of Genes ◽  
Ovarian Folliculogenesis ◽  
Ovary Function

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.

scholarly journals Vascular remodeling by placenta-derived mesenchymal stem cells restores ovarian function in ovariectomized rat model via the VEGF pathway

2020 ◽  
Author(s):  
Jinki Cho ◽  
Tae-Hee Kim ◽  
Jin Seok ◽  
Ji Hye Jun ◽  
Hyeri Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Ovarian Function ◽  
Follicular Development ◽  
Therapeutic Effects ◽  
Vegf Receptor ◽  
Ovx Rats

AbstractAngiogenesis plays an important role in damaged organ or tissue and cell regeneration and ovarian development and function. Primary ovarian insufficiency (POI) is a prevalent pathology in women under 40. Conventional treatment for POI involves hormone therapy. However, due to its side effects, an alternative approach is desirable. Human mesenchymal stem cells (MSCs) from various sources restore ovarian function; however, they have many limitations as stem cell sources. Therefore, it is desirable to study the efficacy of placenta-derived MSCs (PD-MSCs), which possess many advantages over other MSCs, in a rat model of ovarian dysfunction. Here, we investigated the restorative effect of PD-MSCs on injured ovaries in ovariectomized (OVX) rats and the ability of intravenous transplantation (Tx) of PD-MSCs (5 × 105) to enhance ovarian vasculature and follicular development. ELISA analysis of serum revealed that compared to the non-transplantation (NTx) group, the Tx group showed significantly increased levels of anti-Müllerian hormone, follicle stimulating hormone, and estradiol (E2) (*P < 0.05). In addition, histological analysis showed more mature follicles and less atresia and restoration of expanded blood vessels in the ovaries of the OVX PD-MSC Tx group than those of the NTx group (*P < 0.05). Furthermore, folliculogenesis-related gene expression was also significantly increased in the PD-MSC Tx group (*P < 0.05). Vascular endothelial growth factor (VEGF) and VEGF receptor 2 expressions were increased in the ovaries of the OVX PD-MSC Tx group compared to the NTx group through PI3K/AKT/mTOR and GSK3β/β-catenin pathway activation. Interestingly, ex vivo cocultivation of damaged ovaries and PD-MSCs or treatment with recombinant VEGF (50 ng/ml) increased folliculogenic factors and VEGF signaling pathways. Notably, compared to recombinant VEGF, PD-MSCs significantly increased folliculogenesis and angiogenesis (*P < 0.05). These findings suggest that VEGF secreted by PD-MSCs promotes follicular development and ovarian function after OVX through vascular remodeling. Therefore, these results provide fundamental data for understanding the therapeutic effects and mechanism of stem cell therapy based on PD-MSCs and provide a theoretical foundation for their application for obstetrical and gynecological diseases, including infertility and menopause.

scholarly journals Microenvironmental changes induced by placenta-derived mesenchymal stem cells restore ovarian function in ovariectomized rats via activation of the PI3K-FOXO3 pathway

2020 ◽  
Author(s):  
Jong Ho Choi ◽  
Jin Seok ◽  
Seung Mook Lim ◽  
Tae Hee Kim ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Ovarian Function ◽  
Therapeutic Potential ◽  
Ovarian Failure ◽  
Ovariectomized Rats ◽  
Expression Of Genes ◽  
Ovarian Folliculogenesis ◽  
Ovary Function

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.

scholarly journals Microenvironmental changes induced by placenta-derived mesenchymal stem cells restore ovarian function in ovariectomized rats via activation of the PI3K-FOXO3 pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong Ho Choi ◽  
Jin Seok ◽  
Seung Mook Lim ◽  
Tae Hee Kim ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Ovarian Function ◽  
Therapeutic Potential ◽  
Ovarian Failure ◽  
Ovariectomized Rats ◽  
Expression Of Genes ◽  
Ovarian Folliculogenesis ◽  
Ovary Function

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.

scholarly journals Correction: In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model

2021 ◽  
Author(s):  
Xiuying Li ◽  
Zhenhong Wei ◽  
Binxi Li ◽  
Jing Li ◽  
Huiying Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Burn Injury ◽  
Therapeutic Effects

Correction for ‘In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model’ by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861–2872, DOI: 10.1039/C9BM00242A.

scholarly journals Effects of Magnetically Guided, SPIO-Labeled, and Neurotrophin-3 Gene-Modified Bone Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Rui-Ping Zhang ◽  
Ling-Jie Wang ◽  
Sheng He ◽  
Jun Xie ◽  
Jian-Ding Li
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Therapeutic Effects ◽  
Magnetic Targeting ◽  
Bone Mesenchymal Stem Cells ◽  
Cord Injury

Despite advances in our understanding of spinal cord injury (SCI) mechanisms, there are still no effective treatment approaches to restore functionality. Although many studies have demonstrated that transplantingNT3gene-transfected bone marrow-derived mesenchymal stem cells (BMSCs) is an effective approach to treat SCI, the approach is often low efficient in the delivery of engrafted BMSCs to the site of injury. In this study, we investigated the therapeutic effects of magnetic targeting ofNT3gene-transfected BMSCs via lumbar puncture in a rat model of SCI. With the aid of a magnetic targeting cells delivery system, we can not only deliver the engrafted BMSCs to the site of injury more efficiently, but also perform cells imaging in vivo using MR. In addition, we also found that this composite strategy could significantly improve functional recovery and nerve regeneration compared to transplantingNT3gene-transfected BMSCs without magnetic targeting system. Our results suggest that this composite strategy could be promising for clinical applications.

scholarly journals Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Se Ho Kim ◽  
Jae Yeon Kim ◽  
Soo Young Park ◽  
Won Tae Jeong ◽  
Jin Man Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Er Stress ◽  
Rat Model ◽  
Translation Initiation Factor ◽  
Therapeutic Effects ◽  
Stress Markers ◽  
Stress Dependent

Abstract Background Cholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL−1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL−1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL). Methods Liver cirrhosis was induced in Sprague–Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL−1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL−1. Results ER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL−1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p < 0.05). Cocultivation of TG-treated WB-F344 cells with PD-MSCsPRL−1 decreased cytosolic calmodulin (CaM) expression and cytosolic and mitochondrial Ca2+ concentrations. However, the ER Ca2+ concentration was increased compared to PD-MSCs (*p  < 0.05). PRL-1 activated phosphatidylinositol-3-kinase (PI3K) signaling via epidermal growth factor receptor (EGFR), which resulted in calcium increase via CaM expression. Conclusions These findings suggest that PD-MSCsPRL−1 improved hepatic functions via calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.

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