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Management of intrauterine adhesions using human amniotic mesenchymal stromal cells to promote endometrial regeneration and repair through Notch signalling |
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| Authors: | Jie Yu Wenwen Zhang Jiayue Huang Yating Gou Congcong Sun Yingfeng Zhang Yanhua Mao Benyuan Wu Changjiang Li Nizhou Liu Tingting Wang Jiren Huang Jia Wang |
| Institution: | 1. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Resources (equal), Software (equal), Validation (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China;3. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China Contribution: Software (equal);4. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China Contribution: Visualization (equal);5. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China Contribution: Software (equal), Validation (equal);6. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China Contribution: Investigation (equal);7. Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China Contribution: Validation (equal) |
| Abstract: | Intrauterine adhesions (IUAs) severely hamper women's reproductive functions. Human amniotic mesenchymal stromal cell (hAMSC) transplantation is effective in treating IUAs. Here, we examined the function of Notch signalling in IUA treatment with hAMSC transplantation. Forty-five Sprague-Dawley female rats were randomly divided into the sham operation, IUA, IUA + E2, IUA + hAMSCs and IUA + hAMSCs + E2 groups. After IUA induction in the rats, hAMSCs promoted endometrial regeneration and repair via differentiation into endometrial epithelial cells. In all groups, the expression of key proteins in Notch signalling was detected in the uterus by immunohistochemistry. The results indicated Notch signalling activation in the hAMSCs and hAMSCs + E2 groups. We could also induce hAMSC differentiation to generate endometrial epithelial cells in vitro. Furthermore, the inhibition of Notch signalling using the AdR-dnNotch1 vector suppressed hAMSC differentiation (assessed by epithelial and mesenchymal marker levels), whereas its activation using the AdR-Jagged1 vector increased differentiation. The above findings indicate Notch signalling mediates the differentiation of hAMSCs into endometrial epithelial cells, thus promoting endometrial regeneration and repair; Notch signalling could have an important function in IUA treatment. |
| Keywords: | endometrial epithelial cells hAMSCs induction and differentiation intrauterine adhesions Notch signalling pathway |