Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium
Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320424000622 |
| _version_ | 1797215935654789120 |
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| author | Ruomeng Hu Ying Wang Wenwen Li Hongjiang Liu Rong Wu Xuan Xu Xiaohua Jiang Qiong Xing Jianye Wang Zhaolian Wei |
| author_facet | Ruomeng Hu Ying Wang Wenwen Li Hongjiang Liu Rong Wu Xuan Xu Xiaohua Jiang Qiong Xing Jianye Wang Zhaolian Wei |
| author_sort | Ruomeng Hu |
| collection | DOAJ |
| description | Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in endometrial repair remains unexplored. Our investigation focuses on the utilization of HUCBMCs for treating endometrial injury. Methods: The HUCBMCs were isolated from health umbilical cord blood, and co-cultured with the injured endometrial stromal cells and injured endometrial organoids. The cell proliferation and apoptosis were measured by cck8 assays and flow cytometry. Western blotting was used to detect the expression of PTEN, AKT and p-AKT. Immunofluorescence assay revealed expression levels of epithelial-mesenchymal transition (EMT) -related markers such as E-cadherin, N-cadherin, and TGF-β1. The endometrial thickness, fibrosis level, and glandular number were examined after the intravenous injection of HUCBMCs in mouse endometrial models. Immunohistochemistry was employed to assess changes in growth factors vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) as well as fibrosis markers α-SMA and COL1A1. Additionally, expressions of EMT-related proteins E-cadherin and N-cadherin were evaluated. Results: HUCBMCs significantly improved the proliferation and reduced the apoptosis of damaged endometrial stromal cells (ESCs), accompanied by up-regulation of phospho-AKT expression. HUCBMCs increased endometrial thickness and glandular count while decreasing fibrosis and EMT-related markers in mouse endometrial models. Furthermore, EMT-related markers of ESCs and endometrial organoids were significantly decreased. Conclusions: Our findings suggest that HUCBMCs plays a pivotal role in mitigating endometrial injury through the attenuation of fibrosis. HUCBMCs may exert a reverse effect on the EMT process during the endometrium reconstruction. |
| first_indexed | 2024-04-24T11:37:58Z |
| format | Article |
| id | doaj.art-0ebdf4d8c53a40089222942036367f05 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-24T11:37:58Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-0ebdf4d8c53a40089222942036367f052024-04-10T04:29:05ZengElsevierRegenerative Therapy2352-32042024-12-0127279289Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometriumRuomeng Hu0Ying Wang1Wenwen Li2Hongjiang Liu3Rong Wu4Xuan Xu5Xiaohua Jiang6Qiong Xing7Jianye Wang8Zhaolian Wei9Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Corresponding author. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China.Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Corresponding author. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China.Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in endometrial repair remains unexplored. Our investigation focuses on the utilization of HUCBMCs for treating endometrial injury. Methods: The HUCBMCs were isolated from health umbilical cord blood, and co-cultured with the injured endometrial stromal cells and injured endometrial organoids. The cell proliferation and apoptosis were measured by cck8 assays and flow cytometry. Western blotting was used to detect the expression of PTEN, AKT and p-AKT. Immunofluorescence assay revealed expression levels of epithelial-mesenchymal transition (EMT) -related markers such as E-cadherin, N-cadherin, and TGF-β1. The endometrial thickness, fibrosis level, and glandular number were examined after the intravenous injection of HUCBMCs in mouse endometrial models. Immunohistochemistry was employed to assess changes in growth factors vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) as well as fibrosis markers α-SMA and COL1A1. Additionally, expressions of EMT-related proteins E-cadherin and N-cadherin were evaluated. Results: HUCBMCs significantly improved the proliferation and reduced the apoptosis of damaged endometrial stromal cells (ESCs), accompanied by up-regulation of phospho-AKT expression. HUCBMCs increased endometrial thickness and glandular count while decreasing fibrosis and EMT-related markers in mouse endometrial models. Furthermore, EMT-related markers of ESCs and endometrial organoids were significantly decreased. Conclusions: Our findings suggest that HUCBMCs plays a pivotal role in mitigating endometrial injury through the attenuation of fibrosis. HUCBMCs may exert a reverse effect on the EMT process during the endometrium reconstruction.http://www.sciencedirect.com/science/article/pii/S2352320424000622Umbilical cord blood mononuclear cellEndometrial injuryEpithelial-mesenchymal transition (EMT)PTEN-AKT signaling pathwayIntrauterine adhesion |
| spellingShingle | Ruomeng Hu Ying Wang Wenwen Li Hongjiang Liu Rong Wu Xuan Xu Xiaohua Jiang Qiong Xing Jianye Wang Zhaolian Wei Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium Regenerative Therapy Umbilical cord blood mononuclear cell Endometrial injury Epithelial-mesenchymal transition (EMT) PTEN-AKT signaling pathway Intrauterine adhesion |
| title | Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium |
| title_full | Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium |
| title_fullStr | Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium |
| title_full_unstemmed | Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium |
| title_short | Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium |
| title_sort | transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating emt in damaged endometrium |
| topic | Umbilical cord blood mononuclear cell Endometrial injury Epithelial-mesenchymal transition (EMT) PTEN-AKT signaling pathway Intrauterine adhesion |
| url | http://www.sciencedirect.com/science/article/pii/S2352320424000622 |
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