scholarly journals A Combination of Bone Marrow Mesenchymal Stem Cells with Estrogen Improves Rabbit Endometrial Injury Repair by a Mechanism Involved in an Activation of Wnt/β-catenin Signaling

2021 ◽  
Author(s):  
Yuan Liwei ◽  
Cao Jia ◽  
Hu Mingyue ◽  
Xu Dabao ◽  
Li Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Epithelial Cells ◽  
Western Blot ◽  
Signaling Pathway ◽  
Endometrial Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Endometrial Epithelial Cells

Abstract Background: Although the effect of bone marrow mesenchymal stem cells (BMSCs) combined with estrogen therapy in the repair of endometrial injury has been confirmed, its underlying molecular mechanism in intrauterine adhesion (IUA) remains unclear. In this study, we aim to investigate the effect and involvement of a combination of BMSCs with estrogen in restoration of injured endometrium by applying a rabbit endometrial injury model. Method: BMSCs were isolated and labeled with PKH26 fluorescent dye. The IUA animal model was generated by a dual damage method of mechanical curettage and lipopolysaccharide infection. Rabbits were randomly assigned to the following 5 groups: sham operation group, IUA model group, E2 treatment group, BMSCs treatment group, and BMSCs combined with E2 treatment group. Bilateral uterus were obtained at different time points for the further study. HE and Masson staining were used to evaluate the number of endometrial glands and the degree of fibrosis. The expression of fibrosis and EMT related markers were observed by Immunohistochemical, immunofluorescence staining and Western blot. The expression of core molecules in the Wnt/β-catenin signaling pathway was examined by Western blot.Results: In the present study, it is found that PKH26 fluorescent dye can successfully label BMSCs and track the distribution and differentiation of transplanted BMSCs. BMSCs differentiated into endometrial epithelial cells and mainly located around the endometrial glands and extracellular matrix at 3 or 5 days post-transplantation, while BMSCs primarily differentiated into endometrial stromal cells at 7 days after orthotopic transplantation. Furthermore, after combined treatment of BMSCs and estrogen, the number of glands increased significantly, and the area of fibrosis reduced evidently, accompanied by a downregulation of mesenchymal markers and upregulation of epithelial markers when compared with each single treatment group. The expression levels of core molecules in the Wnt/β-catenin signaling pathway were higher in the BMSCs+E2 group than in the other treatment groups. Conclusions: Our study demonstrates that BMSCs combined with estrogen can improve the repair after endometrial injury by promoting the proliferation of endometrial epithelial cells and inhibiting EMT and endometrial fibrosis. This combined effect is achieved in part through activation of the Wnt/β-catenin signaling pathway.

scholarly journals Icariin Regulates the Bidirectional Differentiation of Bone Marrow Mesenchymal Stem Cells through Canonical Wnt Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jun-ming Huang ◽  
Yuan Bao ◽  
Wei Xiang ◽  
Xing-zhi Jing ◽  
Jia-chao Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
Marrow Mesenchymal Stem Cells ◽  
Canonical Wnt

Fat infiltration within the bone marrow is easily observed in some postmenopausal women. Those fats are mainly derived from bone marrow mesenchymal stem cells (BMMSCs). The increment of adipocytes derived from BMMSCs leads to decreased osteoblasts derived from BMMSCs, so the bidirectional differentiation of BMMSCs significantly contributes to osteoporosis. Icariin is the main extractive of Herba Epimedii which is widely used in traditional Chinese medicine. In this experiment, we investigated the effect of icariin on the bidirectional differentiation of BMMSCs through quantitative real-time PCR, immunofluorescence, western blot, and tissue sections in vitro and in vivo. We found that icariin obviously promotes osteogenesis and inhibits adipogenesis through detecting staining and gene expression. Micro-CT analysis showed that icariin treatment alleviated the loss of cancellous bone of the distal femur in ovariectomized (OVX) mice. H&E staining analysis showed that icariin-treated OVX mice obtained higher bone mass and fewer bone marrow lipid droplets than OVX mice. Western blot and immunofluorescence showed that icariin regulates the bidirectional differentiation of BMMSCs via canonical Wnt signaling. This study demonstrates that icariin exerts its antiosteoporotic effect by regulating the bidirectional differentiation of BMMSCs through the canonical Wnt signaling pathway.

Overexpression of Guanine Nucleotide Binding Protein, Alpha Stimulating (GNAS) Regulates Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in High Glucose Environment by Regulating ERK/P38 Signaling Pathway

2020 ◽  
Vol 10 (2) ◽  
pp. 259-264
Author(s):  
Wei Zhang ◽  
Yuanbo Wang ◽  
Song Jin ◽  
Hui Xin ◽  
Changxin Wang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Signaling Pathway ◽  
High Glucose ◽  
Caspase 3 ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) can treat osteoporosis. Whether GNAS affects BMSCs osteogenic differentiation under high glucose condition is unknown. Rat BMSCs were isolated and randomly divided into control group, high glucose group and GNAS group. The BMSCs were transfected with GNAS plasmid in high glucose environment followed by analysis of GNAS expression by Real time PCR and Western blot, BMSCs proliferation by MTT assay, Caspase 3 activity, ALP activity, formation of calcified nodules by alizarin red staining, OC and BMP-2 expression by Real time PCR and expression of ERK/P38 signaling pathway protein by Western blot. In high glucose environment, GNAS expression was significantly decreased, cell proliferation was inhibited, Caspase 3 activity was increased, along with decreased ALP activity, calcified nodules formation and expression of OC, BMP-2, p-ERK1/2 and p-P38 (P < 0.05). GNAS plasmid transfected into high glucose environment BMSCs can significantly promote GNAS expression and cell proliferation, decrease Caspase 3 activity, increase p-ERK1/2 and p-P38 expression, ALP activity and calcified nodules formation as well as increase OC and BMP-2 expression (P < 0.05). GNAS1 expression is decreased in BMSCs cells in a high glucose environment. Overexpression of GNAS1 can inhibit the apoptosis of BMSCs by regulating the ERK/P38 signaling pathway, promote its proliferation and differentiation into osteogenic direction.

Down-Regulation of p38 Mitogen-Activated Protein Kinases/Nuclear Factor Kappa Light Chain Enhancer of Activated B Cells (p38 MAPK/NF-κB) Signaling Pathway Promotes Bone Marrow Mesenchymal Stem Cells Differentiation into Neural Stem Cells in Healing Neurodegeneration

2022 ◽  
Vol 12 (3) ◽  
pp. 653-658
Author(s):  
Xin Yang ◽  
Shandan Wang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Neural Stem Cells ◽  
Western Blot ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Healthy Controls ◽  
Mitogen Activated Protein ◽  
Marrow Mesenchymal Stem Cells

This study intends to promote bone marrow mesenchymal stem cells (BMSCs) differentiation into neural stem cells by down-regulating p38 MAPK/NF-κB to heal neurodegeneration. 26 patients with neurodegenerative diseases were enrolled from the Department of Neurology along with recruitment of 26 other healthy controls followed by analysis of p38 MAPK/NF-κB signaling pathway expression by ELISA. BMSCs were cultured and characterized by flow cytometry. Western blot and qRTPCR measured the p38 MAPK/NF-κB expression in the absence or presence of p38 MAPK/NF-κB inhibitors. p38 MAPK/NF-κB expression in 26 neurodegenerative patients was significantly higher than that of 26 healthy controls. The qRT-PCR and western blot results showed that the neural stem cell-specific proteins expression was increased as days went; after addition of p38 MAPK/NF-κB inhibitor, the expression of related specific genes were significantly decreased. In conclusion, inhibition of the expression of p38 MAPK/NF-κB signaling pathway can heal neurodegeneration by promoting the differentiation of BMSCs into neural stem cells.

Stem Cells and Endometrial Regeneration: From Basic Research to Clinical Trial

2019 ◽  
Vol 14 (4) ◽  
pp. 293-304 ◽  
Author(s):  
Xinxin Zhu ◽  
Bruno Péault ◽  
Guijun Yan ◽  
Haixiang Sun ◽  
Yali Hu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Basic Research ◽  
Alternative Source ◽  
Endometrial Stem Cells ◽  
Endometrial Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Monthly Changes

Monthly changes in the endometrial cycle indicate the presence of endometrial stem cells. In recent years, various stem cells that exist in the endometrium have been identified and characterized. Additionally, many studies have shown that Bone Marrow Mesenchymal Stem Cells (BM-MSCs) provide an alternative source for regenerating the endometrium and repairing endometrial injury. This review discusses the origin of endometrial stem cells, the characteristics and main biomarkers among five types of putative endometrial stem cells, applications of endometrium-derived stem cells and menstrual blood-derived stem cells, the association between BM-MSCs and endometrial stem cells, and progress in repairing endometrial injury.

scholarly journals Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jianjun Wu ◽  
Shoupin Xie ◽  
Hailong Li ◽  
Yanxia Zhang ◽  
Jia Yue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Nude Mice ◽  
Antitumor Effect ◽  
Tumor Tissue ◽  
Model Group ◽  
Nude Mouse Model ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice Methods The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured Results There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) Conclusions This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.

miR-1 Activates NF-κB to Promote the Differentiation of Bone Marrow Mesenchymal Stem Cells in Mouse Models of Glioma

2021 ◽  
Vol 11 (7) ◽  
pp. 1327-1332
Author(s):  
Long Zhou ◽  
Kui Wang ◽  
Meixia Liu ◽  
Wen Wei ◽  
Liu Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Mouse Models ◽  
Cell Apoptosis ◽  
Bone Diseases ◽  
Control Group ◽  
Marrow Mesenchymal Stem Cells ◽  
And Control

NF-κB activation and its abnormal expression are involved in the progression of glioma. miRNA plays a crucial role in bone diseases. The role of NF-κB is becoming more and more important. The purpose of this study is to explore the mechanism by how miR-1 regulates NF-κB signaling. C57 glioma mouse models were divided into osteoporosis (OP) group and control group. qPCR was used to measure miR-1 levels in OP and control mice. Bone marrow mesenchymal stem cells (BMSCs) were cultured and transfected with miR-1 specific siRNA to establish miR-1 knockout cell model followed by analysis of cell apoptosis, expression of NF-κB signaling molecules by western blot. qPCR results showed that miR-1 levels in OP mice were significantly reduced compared to control mice. A large number of siRNA particles were observed in transfected BMSCs under a fluorescence microscope. qPCR results showed that siRNA transfection significantly suppressed miR-1, indicating successful transfection. Flow cytometry revealed significant differences in cell apoptosis between miR-1 siRNA group and the NC group. Western blot indicated miR-1 promoted BMSCs differentiation via NF-κB mediated up-regulation of ALP activity. The expression of miR-1 is low in BMSCs of mice with glioma. In addition, BMSCs differentiation is enhanced by NF-κB activation via up-regulating miR-1.

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