scholarly journals Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Activate PTEN/AKT Pathway and Promote Repair of Damaged Endometrium

Author(s):  
Jianye Wang ◽  
Liu Dong ◽  
Xuan Xu ◽  
Xiaohua Jiang ◽  
Ziwei Li ◽  
...  

Abstract BackgroundEndometrial injury contributes to impaired endometrial receptivity, and is well recognized as a critical factor in implantation failure. Increasing evidence suggests that the therapeutic effects of mesenchymal stem cells (MSCs) mainly depend on their capacity to secrete paracrine factors and are mediated by MSC-derived exosomes (MSC-Exos). In this study, we aimed to explore the effects of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) on injured endometrium in the mouse endometrial damage model and the potential mechanisms for these effects.MethodsAll female mice were randomly divided into control group, saline group, and exosome group. To observe the distribution of exosomes in vivo, DiR-labeled hUCMSC-Exos were injected into the tail vein of endometrium-injured mice. HE staining was used to detect changes in endometrial thickness and number of glands. TUNEL staining was used to detect cells apoptosis. The expression of Ki67 and CD31 was examined by immunohistochemistry. Then, western blotting was used to measure the expression of Bcl-2, Bax, Cleaved Caspase-3, PTEN, AKT and p-AKT. The expression of VEGF and IGF-1 was detected by RT-PCR.ResultshUCMSC-Exos was able to migrate to the damaged endometrium. After hUCMSC-Exos injection, the endometrial thickness and the number of glands were significantly increased (P< 0.05). Compared with the saline group, apoptosis was significantly reduced in the exosome group, and the expression of Ki67 and CD31 was significantly increased (P< 0.05). Besides, the expression of Bax, Cleaved Caspase-3 and PTEN was reduced as hUCMSC-Exos addition, and the Bcl-2 and p-Akt expression was increased. The expression of VEGF and IGF-1 was significantly upregulated in the exosome group compared to the saline group (P< 0.05).ConclusionshUCMSC-Exos ameliorated the damaged uterus, increased endometrial thickness, suppressed apoptosis and improved the cell proliferation in the mouse injured endometrium model. Furthermore, we discovered that hUCMSC-Exos could activate the PTEN/AKT signaling pathways and induce the overexpression of VEGF and IGF-1 in vivo.

2012 ◽  
Vol 21 (18) ◽  
pp. 3289-3297 ◽  
Author(s):  
Hong-Chao Zhang ◽  
Xin-Bin Liu ◽  
Shu Huang ◽  
Xiao-Yun Bi ◽  
Heng-Xiang Wang ◽  
...  

2019 ◽  
Vol 28 (12) ◽  
pp. 1552-1559 ◽  
Author(s):  
Jianwei Xu ◽  
Zhanhui Feng ◽  
Xianyao Wang ◽  
Ying Xiong ◽  
Lan Wang ◽  
...  

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Li Jinfeng ◽  
Wang Yunliang ◽  
Liu Xinshan ◽  
Wang Yutong ◽  
Wang Shanshan ◽  
...  

The purpose of this study is to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) activated by curcumin (CUR) on PC12 cells induced by 1-methyl-4-phenylpyridinium ion (MPP+), a cell model of Parkinson’s disease (PD). The supernatant of hUC-MSC and hUC-MSC activated by 5 µmol/L CUR (hUC-MSC-CUR) were collected in accordance with the same concentration. The cell proliferation and differentiation potential to dopaminergic neuronal cells and antioxidation were observed in PC12 cells after being treated with the above two supernatants and 5 µmol/L CUR. The results showed that the hUC-MSC-CUR could more obviously promote the proliferation and the expression of tyrosine hydroxylase (TH) and microtubule associated protein-2 (MAP2) and significantly decreased the expression of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in PC12 cells. Furtherly, cytokines detection gave a clue that the expression of IL-6, IL-10, and NGF was significantly higher in the group treated with the hUC-MSC-CUR compared to those of other two groups. Therefore, the hUC-MSC-CUR may be a potential strategy to promote the proliferation and differentiation of PD cell model, therefore providing new insights into a novel therapeutic approach in PD.


2018 ◽  
Vol 373 (2) ◽  
pp. 379-393 ◽  
Author(s):  
Tao Zhang ◽  
Pan Wang ◽  
Yanxia Liu ◽  
Jiankang Zhou ◽  
Zhenqing Shi ◽  
...  

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.


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