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      Umbilical cord-derived mesenchymal stem cell transplantation in vaginal replacement in vitro and in a rat model

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          Abstract

          Cell transplantation strategies represent a potential therapeutic approach towards repair of congenital vaginal agenesis. In this study, the efficacy and mechanisms of action of treatment with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on vaginal regeneration was explored. UC-MSC transplantation alone, small intestinal submucosal (SIS) grafting alone, and a combination of UC-MSC transplantation/SIS grafting were performed with a vaginal defect rat model. Histological analyses of tissue sections were subsequently performed. UC-MSCs promoted the recovery of keratinizing squamous epithelium and papillae to nearly the same levels as in normal tissue. Of the treatments tested, UC-MSC transplantation showed optimal performance in inhibiting collagen deposition and accelerating the synthesis of elastin to maintain tissue elasticity. UC-MSC treatment also increased Cyclin D1, Ki67, and CD31 expression as assessed by immunohistochemistry. We also investigated the effects of UC-MSC secretions on keratinocytes in a co-culture model. UC-MSCs significantly stimulated vaginal tissue repair by promoting vaginal epithelium regeneration via paracrine factors but not by exploiting their keratinocyte differentiation potential. Further, UC-MSCs facilitated epithelial cell viability and promoted cell cycle progression via the AKT/GSK3β/Cyclin D1 pathway. These results indicate that UC-MSC transplantation is a feasible approach for vaginal tissue regeneration.

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          Author and article information

          Journal
          Am J Transl Res
          Am J Transl Res
          ajtr
          American Journal of Translational Research
          e-Century Publishing Corporation
          1943-8141
          2018
          15 November 2018
          : 10
          : 11
          : 3762-3772
          Affiliations
          [1 ] Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai, P. R. China
          [2 ] Shanghai Medical College, Fudan University Shanghai, P. R. China
          [3 ] Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University Shanghai, P. R. China
          [4 ] Alliancells Institute of Stem Cells and Translational Regenerative Medicine Tianjin 300308, P. R. China
          Author notes
          Address correspondence to: Yongjun Liu, Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin 300308, P. R. China. Tel: +86 18920692888; E-mail: Yongjunliu323@ 123456gmail.com ; Jingxin Ding, Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, 419 Fang Xie Road, Shanghai 200011, P. R. China. Tel: +86 13918206746; Fax: +86 21 63455050; E-mail: djxdd@ 123456fudan.edu.cn
          Article
          PMC6291690 PMC6291690 6291690
          6291690
          30662626
          d2553e5e-187f-41f2-bf68-4296d3611edd
          AJTR Copyright © 2018
          History
          : 09 May 2018
          : 16 October 2018
          Categories
          Original Article

          tissue repair,Vaginal regeneration,human umbilical cord-derived mesenchymal stem cells,paracrine factors,keratinocytes,AKT/GSK3β/Cyclin D1 pathway

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