Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium
Abstract Purpose The fundamental cause of intrauterine adhesions (IUAs) is the destruction and reduction in stem cells in endometrial basal layer, resulting in endometrial reconstruction very difficult. The purpose of this study was to investigate the effects and underlying mechanism of human umbili...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-02990-1 |
| _version_ | 1818197099530944512 |
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| author | Qing Hua Yong Zhang Hongjuan Li Haoran Li Ranran Jin Li Li Yuancui Xiang Meng Tian Jingjing Wang Lei Sun Yali Wang |
| author_facet | Qing Hua Yong Zhang Hongjuan Li Haoran Li Ranran Jin Li Li Yuancui Xiang Meng Tian Jingjing Wang Lei Sun Yali Wang |
| author_sort | Qing Hua |
| collection | DOAJ |
| description | Abstract Purpose The fundamental cause of intrauterine adhesions (IUAs) is the destruction and reduction in stem cells in endometrial basal layer, resulting in endometrial reconstruction very difficult. The purpose of this study was to investigate the effects and underlying mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on the endometrial reconstruction after transplantation. Methods hUCB-MSCs were isolated and identified by flow cytometry, osteogenic, adipogenic and chondrogenic differentiation assays. The rabbit IUA models were established and set five groups (control, 14/28th day after surgery, estrogen and hUCB-MSCs treatment). The number of endometrial glands and the fibrosis rate were evaluated using HE and Masson staining, respectively. Endometrial proliferation, angiogenesis and inflammation were evaluated by immunohistochemical staining of ER, Ki-67and TGF-β1, respectively. Single-cell RNA sequencing (scRNA-seq) was applied to explore the cell differentiation trajectory after hUCB-MSCs transplanted into IUA endometrium. Finally, molecular mechanism of hUCB-MSCs repairing damaged endometrium was investigated by RNA sequencing, qRT-PCR and Western blot assays. Results After transplantation of the hUCB-MSCs, the increase in endometrial gland number, estrogen receptor (ER) and Ki-67 expression, and the decrease in fibrosis rate and TGF-β expression (P < 0.05), suggested the endometrial repair, angiogenesis and inflammatory suppression. The therapeutic effect of hUCB-MSCs was significantly improved compared with 28th day after surgery and estrogen group. ScRNA-seq demonstrated that the transplanted hUCB-MSCs can trans-differentiate into endometrial cells: epithelial, fibroblast and macrophage. RNA sequencing of six IUA samples combined with qRT-PCR and Western blot assays further revealed that hUCB-MSCs may regulate Th17/Treg balance through NF-κB signaling, thus inhibiting the immune response of damaged endometrium. Conclusions Our study demonstrated that hUCB-MSCs can repair damaged endometrium through trans-differentiation, immunomodulatory capacities and NF-κB signaling, suggesting the treatment value of hUCB-MSCs in IUA. |
| first_indexed | 2024-12-12T01:44:35Z |
| format | Article |
| id | doaj.art-8e642e0ab2514c89b7e0cb2fe08f7ff2 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T01:44:35Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-8e642e0ab2514c89b7e0cb2fe08f7ff22022-12-22T00:42:37ZengBMCStem Cell Research & Therapy1757-65122022-07-0113111510.1186/s13287-022-02990-1Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometriumQing Hua0Yong Zhang1Hongjuan Li2Haoran Li3Ranran Jin4Li Li5Yuancui Xiang6Meng Tian7Jingjing Wang8Lei Sun9Yali Wang10Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityBranch Center of Advanced Medical Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityAbstract Purpose The fundamental cause of intrauterine adhesions (IUAs) is the destruction and reduction in stem cells in endometrial basal layer, resulting in endometrial reconstruction very difficult. The purpose of this study was to investigate the effects and underlying mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on the endometrial reconstruction after transplantation. Methods hUCB-MSCs were isolated and identified by flow cytometry, osteogenic, adipogenic and chondrogenic differentiation assays. The rabbit IUA models were established and set five groups (control, 14/28th day after surgery, estrogen and hUCB-MSCs treatment). The number of endometrial glands and the fibrosis rate were evaluated using HE and Masson staining, respectively. Endometrial proliferation, angiogenesis and inflammation were evaluated by immunohistochemical staining of ER, Ki-67and TGF-β1, respectively. Single-cell RNA sequencing (scRNA-seq) was applied to explore the cell differentiation trajectory after hUCB-MSCs transplanted into IUA endometrium. Finally, molecular mechanism of hUCB-MSCs repairing damaged endometrium was investigated by RNA sequencing, qRT-PCR and Western blot assays. Results After transplantation of the hUCB-MSCs, the increase in endometrial gland number, estrogen receptor (ER) and Ki-67 expression, and the decrease in fibrosis rate and TGF-β expression (P < 0.05), suggested the endometrial repair, angiogenesis and inflammatory suppression. The therapeutic effect of hUCB-MSCs was significantly improved compared with 28th day after surgery and estrogen group. ScRNA-seq demonstrated that the transplanted hUCB-MSCs can trans-differentiate into endometrial cells: epithelial, fibroblast and macrophage. RNA sequencing of six IUA samples combined with qRT-PCR and Western blot assays further revealed that hUCB-MSCs may regulate Th17/Treg balance through NF-κB signaling, thus inhibiting the immune response of damaged endometrium. Conclusions Our study demonstrated that hUCB-MSCs can repair damaged endometrium through trans-differentiation, immunomodulatory capacities and NF-κB signaling, suggesting the treatment value of hUCB-MSCs in IUA.https://doi.org/10.1186/s13287-022-02990-1Intrauterine adhesion (IUA)Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs)scRNA-seqTrans-differentiationNF-κB signaling |
| spellingShingle | Qing Hua Yong Zhang Hongjuan Li Haoran Li Ranran Jin Li Li Yuancui Xiang Meng Tian Jingjing Wang Lei Sun Yali Wang Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium Stem Cell Research & Therapy Intrauterine adhesion (IUA) Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) scRNA-seq Trans-differentiation NF-κB signaling |
| title | Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium |
| title_full | Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium |
| title_fullStr | Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium |
| title_full_unstemmed | Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium |
| title_short | Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium |
| title_sort | human umbilical cord blood derived mscs trans differentiate into endometrial cells and regulate th17 treg balance through nf κb signaling in rabbit intrauterine adhesions endometrium |
| topic | Intrauterine adhesion (IUA) Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) scRNA-seq Trans-differentiation NF-κB signaling |
| url | https://doi.org/10.1186/s13287-022-02990-1 |
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