scholarly journals Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jianye Wang ◽  
Ruomeng Hu ◽  
Qiong Xing ◽  
Xinghao Feng ◽  
Xiaohua Jiang ◽  
...  

The human endometrial stromal cells (hEndoSCs) could maintain endometrial homeostasis and play a critical role in repairing endometrial injury. Mesenchymal stem cells (MSCs) significantly increase the proliferation of damaged hEndoSCs and protect them from apoptosis. Recent studies indicated that exosomes derived from stem cells could be recruited to damaged tissues for regeneration, which exhibit the potential for stem cell therapy as therapeutic vectors. In this study, we isolated human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and investigated the effects of hUCMSC-Exos on mifepristone-induced hEndoSC injury. Exosome uptake and cell proliferation as well as cell apoptosis of damaged hEndoSCs treated with hUCMSC-Exos were detected. We also assessed the expression of apoptosis-related proteins and the PTEN/AKT signaling pathway. We found hUCMSC-Exos improved the proliferation of damaged hEndoSCs and protected hEndoSCs from the mifepristone-induced apoptosis. hUCMSC-Exos upregulated Bcl-2 level as well as downregulated Cleaved Caspase-3 level and activated the PTEN/AKT signaling pathway to regulate the proliferation and antiapoptosis. These results indicated hUCMSC-Exos protected hEndoSCs from mifepristone-induced apoptosis and played an active role in repairing the damaged hEndoSCs through the PTEN/AKT signaling pathway in vitro. hUCMSC-Exos may hold great promise in the cell-free therapy of endometrial injury.

2021 ◽  
Author(s):  
Shi-wei Ren ◽  
Yang Song ◽  
Qing-run Zhu ◽  
Min-gang He ◽  
Jie Qiu ◽  
...  

Abstract BackgroundPostmenopausal osteoporosis (PMO) is a relatively common disease characterized by low bone mass and microstructural changes of trabecular bone. The reduced bone strength is caused a variety of complications, including fragility fracture and sarcopenia.MethodsWe used CCK-8 and EdU assays to evaluate cell proliferation rates. The osteogenesis effect was detected using ALP staining, alizarin red staining, and q-PCR. In vivo, the effects of exosomes derived from HUC-MSCs were evaluated using HE staining, IHC staining and Masson staining. In addition, we explored the mechanism of exosomes and found that the AKT signaling pathway played an important role in osteogenesis and cell proliferation.ResultsThis paper mainly explored the function of exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) and provided a new strategy for the treatment of postmenopausal osteoporosis. ConclusionsIn conclusion, exogenous administration of exosomes can contribute to the treatment postmenopausal osteoporosis to a certain extent.


2020 ◽  
Vol 29 ◽  
pp. 096368972092999 ◽  
Author(s):  
Guanghui Xiu ◽  
Xiuling Li ◽  
Yunyu Yin ◽  
Jintao Li ◽  
Bingqin Li ◽  
...  

Mesenchymal stem cells (MSCs) are thought to have great potential in the therapy of acute liver injury. It is possible that these cells may be regulated by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling axis, which has been shown to promote stem cells migration in the inflammation-associated diseases. However, the effects of SDF-1/CXCR4 axis on the MSCs-transplantation-based treatment for acute liver injury and the underlying mechanisms are largely unknown. In this study, we sought to determine whether SDF-1/CXCR4 would augment the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) by promoting their migration, which may result from activating the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, in a rat acute liver injury model induced by lipopolysaccharide (LPS). We found that BMSCs transplantation markedly attenuated liver injury and improved the survival of LPS-treated rats. Of interest, overexpression of CXCR4 in BMSCs could substantially promote their migration both in vitro and in vivo, and result in even better therapeutic effects. This might be attributed to the activation of PI3K/Akt signaling pathway in BMSCs that is downstream of CXCR4, as demonstrated by the use of the CXCR4 antagonist AMD3100 and PI3K pathway inhibitor LY294002 assays in vitro and in vivo. Together, our results unraveled a novel molecular mechanism for the therapeutic effect of BMSCs for the treatment of acute liver injury, which may shed a new light on the clinical application of BMSCs for acute liver failure.


2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chenyi Ye ◽  
Wei Zhang ◽  
Kai Hang ◽  
Mo Chen ◽  
Weiduo Hou ◽  
...  

Abstract Interleukin (IL)-37, a pivotal anti-inflammatory cytokine and a fundamental inhibitor of innate immunity, has recently been shown to be abnormally expressed in several autoimmune-related orthopedic diseases, including rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. However, the role of IL-37 during osteogenic differentiation of mesenchymal stem cells (MSCs) remains largely unknown. In this study, extracellular IL-37 significantly increased osteoblast-specific gene expression, the number of mineral deposits, and alkaline phosphatase activity of MSCs. Moreover, a signaling pathway was activated in the presence of IL-37. The enhanced osteogenic differentiation of MSCs due to supplementation of IL-37 was partially rescued by the presence of a PI3K/AKT signaling inhibitor. Using a rat calvarial bone defect model, IL-37 significantly improved bone healing. Collectively, these findings indicate that extracellular IL-37 enhanced osteogenesis of MSCs, at least in part by activation of the PI3K/AKT signaling pathway.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Feng Gao ◽  
Sheng-Li Xia ◽  
Xiu-Hui Wang ◽  
Xiao-Xiao Zhou ◽  
Jun Wang

Abstract Background Osteoporosis is a common disease closely associated with aging. In this study, we aimed to investigate the role of Cornuside I in promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the potential mechanism. Methods BMSCs were isolated and treated with different concentrations of Cornuside I (0, 10, 30, 60 μM). Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. RNA sequencing was performed on the isolated BMSCs with control and Cornuside I treatment. Differentially expressed genes were obtained by the R software. Alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR and western blot were used to detect the expression of osteoblast markers. Results Cornuside I treatment significantly improved BMSC proliferation. The optimal dose of Cornuside I was 30 μM (P < 0.05). Cornuside I dose dependently increased the ALP activity and calcium deposition than control group (P < 0.05). A total of 704 differentially expressed genes were identified between Cornuside I and normal BMSCs. Cornuside I significantly increased the PI3K and Akt expression. Moreover, the promotion effects of Cornuside I on osteogenic differentiation of BMSCs were partially blocked by PI3K/Akt inhibitor, LY294002. Conclusion Cornuside I plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of PI3K/Akt signaling pathway.


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