Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions
Abstract Background Intrauterine adhesion (IUA), resulting from uterine trauma, is one of the major causes of female infertility. Previous studies have demonstrated that endometrial mesenchymal stem cells (eMSC) have therapeutic effects on IUA through cellular secretions. It is particularly true for...
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BMC
2024-12-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-024-04100-9 |
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| author | Kai Chen Yanyan Gao Ninuo Xia Yusheng Liu Huiru Wang Hui Ma Shengxia Zheng Fang Fang |
| author_facet | Kai Chen Yanyan Gao Ninuo Xia Yusheng Liu Huiru Wang Hui Ma Shengxia Zheng Fang Fang |
| author_sort | Kai Chen |
| collection | DOAJ |
| description | Abstract Background Intrauterine adhesion (IUA), resulting from uterine trauma, is one of the major causes of female infertility. Previous studies have demonstrated that endometrial mesenchymal stem cells (eMSC) have therapeutic effects on IUA through cellular secretions. It is particularly true for most of the pre-clinical experiments performed on multiple animal models, as human-derived eMSC cannot maintain long-term engraftment in animals. Whether tissue-specific MSCs from allogeneic origin can engraft and exert long-term therapeutic efficacy has yet to be thoroughly explored. Methods We established a rat IUA model to study the long-term engraftment and therapeutic effects of eMSC derived from humans and rats. Human and rat eMSC were isolated and verified by the expression of cell surface markers and the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. The cells were then labeled by green fluorescence proteins (GFP) and transplanted to the rat uterus ex vivo and in vivo. The engraftment was investigated by the expression of GFP at different days after transplantation. Assessed the therapeutic effects by examining the endometrial thickness, the number of glands, and the pregnancy outcome. Significantly, we conducted a thorough assessment of the local cellular immune response following both xenograft and allograft transplantation. Results H-eMSC were eliminated by rats’ immune systems within three days after transplantation. In constrast, R-eMSC successfully engrafted and persisted in rat tissue for over ten days. Notably, R-eMSC significantly improved the pregnancy rate by enhancing endometrial thickness and increasing the number of glands, while also reducing fibrosis in rat IUA models. Additionally, the immune response to R-eMSC was generally less aggressive compared to that of xenogeneic MSCs. Conclusions Tissue-specific MSCs from the allogeneic origin can integrate into the repaired tissue and exert long-term therapeutic efficacy in the model of IUA. This study indicates that in addition to secreting therapeutic factors short-time, tissue-specific MSCs may engraft and participate in long-time tissue repair and regeneration. |
| format | Article |
| id | doaj-art-2548d7fff0504876843a5ef22c3d09a5 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-2548d7fff0504876843a5ef22c3d09a52024-12-29T12:12:13ZengBMCStem Cell Research & Therapy1757-65122024-12-0115111310.1186/s13287-024-04100-9Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesionsKai Chen0Yanyan Gao1Ninuo Xia2Yusheng Liu3Huiru Wang4Hui Ma5Shengxia Zheng6Fang Fang7Reproductive Medicine Center and Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAnhui Tianlun Infertility Specialist HospitalThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAnhui Tianlun Infertility Specialist HospitalReproductive Medicine Center and Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaReproductive Medicine Center and Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract Background Intrauterine adhesion (IUA), resulting from uterine trauma, is one of the major causes of female infertility. Previous studies have demonstrated that endometrial mesenchymal stem cells (eMSC) have therapeutic effects on IUA through cellular secretions. It is particularly true for most of the pre-clinical experiments performed on multiple animal models, as human-derived eMSC cannot maintain long-term engraftment in animals. Whether tissue-specific MSCs from allogeneic origin can engraft and exert long-term therapeutic efficacy has yet to be thoroughly explored. Methods We established a rat IUA model to study the long-term engraftment and therapeutic effects of eMSC derived from humans and rats. Human and rat eMSC were isolated and verified by the expression of cell surface markers and the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. The cells were then labeled by green fluorescence proteins (GFP) and transplanted to the rat uterus ex vivo and in vivo. The engraftment was investigated by the expression of GFP at different days after transplantation. Assessed the therapeutic effects by examining the endometrial thickness, the number of glands, and the pregnancy outcome. Significantly, we conducted a thorough assessment of the local cellular immune response following both xenograft and allograft transplantation. Results H-eMSC were eliminated by rats’ immune systems within three days after transplantation. In constrast, R-eMSC successfully engrafted and persisted in rat tissue for over ten days. Notably, R-eMSC significantly improved the pregnancy rate by enhancing endometrial thickness and increasing the number of glands, while also reducing fibrosis in rat IUA models. Additionally, the immune response to R-eMSC was generally less aggressive compared to that of xenogeneic MSCs. Conclusions Tissue-specific MSCs from the allogeneic origin can integrate into the repaired tissue and exert long-term therapeutic efficacy in the model of IUA. This study indicates that in addition to secreting therapeutic factors short-time, tissue-specific MSCs may engraft and participate in long-time tissue repair and regeneration.https://doi.org/10.1186/s13287-024-04100-9Intrauterine adhesionEndometrial mesenchymal stem cellsStem cell therapyAnimal model |
| spellingShingle | Kai Chen Yanyan Gao Ninuo Xia Yusheng Liu Huiru Wang Hui Ma Shengxia Zheng Fang Fang Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions Stem Cell Research & Therapy Intrauterine adhesion Endometrial mesenchymal stem cells Stem cell therapy Animal model |
| title | Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions |
| title_full | Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions |
| title_fullStr | Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions |
| title_full_unstemmed | Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions |
| title_short | Long-term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions |
| title_sort | long term therapeutic effects of allogeneic mesenchymal stem cell transplantation for intrauterine adhesions |
| topic | Intrauterine adhesion Endometrial mesenchymal stem cells Stem cell therapy Animal model |
| url | https://doi.org/10.1186/s13287-024-04100-9 |
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