Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing
Abstract Background Increasing evidence suggests that mesenchymal stem cells (MSCs) repair traumatized tissues primarily through paracrine secretion and differentiation into specific cell types. However, the role of epithelial differentiation of MSCs in cutaneous wound healing is unclear. This study...
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BMC
2024-11-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-024-04081-9 |
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| author | Yongzheng Li Lingling Dong Yani Chen Wenjin Cai Guoli Yang Ying Wang |
| author_facet | Yongzheng Li Lingling Dong Yani Chen Wenjin Cai Guoli Yang Ying Wang |
| author_sort | Yongzheng Li |
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| description | Abstract Background Increasing evidence suggests that mesenchymal stem cells (MSCs) repair traumatized tissues primarily through paracrine secretion and differentiation into specific cell types. However, the role of epithelial differentiation of MSCs in cutaneous wound healing is unclear. This study aimed to investigate the epithelial differentiation potential of gingival tissue-derived MSCs (GMSCs) in epithelial cell growth medium and the mechanisms underlying their differentiation into an epithelial-like cell phenotype. Methods We used scanning electron microscopy to examine GMSCs for epithelial differentiation. Quantitative real-time polymerase chain reaction and Western blotting were respectively used to measure genes and proteins related to epithelial differentiation. Immunofluorescence was used to examine subcellular localization of KLF4, KRT19, and β-catenin proteins. Transcriptome sequencing was used to enrich the mechanisms underlying epithelial differentiation in GMSCs. An MSAB inhibitor was used to validate the Wnt signaling pathway further. The wound healing rate and re-epithelialization were assessed through macroscopical observation and hematoxylin and eosin staining. Results GMSCs cultured in epithelial cell growth medium from days 3 to 15 exhibited decreased expression of mesenchymal-epithelial transition and stemness-related proteins (N-cadherin, Vimentin, KLF4, and SOX2), increased expression of epithelial-related proteins (KRT12, KRT15, KRT19, and E-cadherin), and exhibited epithelial-like morphology. Mechanistically, high-throughput sequencing revealed that the Wnt and TGF-beta signaling pathways were inhibited during epithelial differentiation of GMSCs (Epi-GMSCs). MSAB-induced Wnt signaling pathway inhibition promoted epithelial-related gene and protein expression. Furthermore, we demonstrated the ability of Epi-GMSCs to facilitate wound healing by improving re-epithelialization in a full-thickness skin defect model. Conclusions Collectively, this study uncovers that GMSCs have the ability to differentiate into epithelia and highlights a promising strategy for using Epi-GMSCs to improve cutaneous wound healing. |
| format | Article |
| id | doaj-art-6ec571976d9f47bc8c97a1f66e1725ad |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-6ec571976d9f47bc8c97a1f66e1725ad2024-12-01T12:12:52ZengBMCStem Cell Research & Therapy1757-65122024-11-0115111410.1186/s13287-024-04081-9Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healingYongzheng Li0Lingling Dong1Yani Chen2Wenjin Cai3Guoli Yang4Ying Wang5Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang UniversityStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang UniversityStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang UniversityStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang UniversityStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang UniversityStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang UniversityAbstract Background Increasing evidence suggests that mesenchymal stem cells (MSCs) repair traumatized tissues primarily through paracrine secretion and differentiation into specific cell types. However, the role of epithelial differentiation of MSCs in cutaneous wound healing is unclear. This study aimed to investigate the epithelial differentiation potential of gingival tissue-derived MSCs (GMSCs) in epithelial cell growth medium and the mechanisms underlying their differentiation into an epithelial-like cell phenotype. Methods We used scanning electron microscopy to examine GMSCs for epithelial differentiation. Quantitative real-time polymerase chain reaction and Western blotting were respectively used to measure genes and proteins related to epithelial differentiation. Immunofluorescence was used to examine subcellular localization of KLF4, KRT19, and β-catenin proteins. Transcriptome sequencing was used to enrich the mechanisms underlying epithelial differentiation in GMSCs. An MSAB inhibitor was used to validate the Wnt signaling pathway further. The wound healing rate and re-epithelialization were assessed through macroscopical observation and hematoxylin and eosin staining. Results GMSCs cultured in epithelial cell growth medium from days 3 to 15 exhibited decreased expression of mesenchymal-epithelial transition and stemness-related proteins (N-cadherin, Vimentin, KLF4, and SOX2), increased expression of epithelial-related proteins (KRT12, KRT15, KRT19, and E-cadherin), and exhibited epithelial-like morphology. Mechanistically, high-throughput sequencing revealed that the Wnt and TGF-beta signaling pathways were inhibited during epithelial differentiation of GMSCs (Epi-GMSCs). MSAB-induced Wnt signaling pathway inhibition promoted epithelial-related gene and protein expression. Furthermore, we demonstrated the ability of Epi-GMSCs to facilitate wound healing by improving re-epithelialization in a full-thickness skin defect model. Conclusions Collectively, this study uncovers that GMSCs have the ability to differentiate into epithelia and highlights a promising strategy for using Epi-GMSCs to improve cutaneous wound healing.https://doi.org/10.1186/s13287-024-04081-9Gingival mesenchymal stem cellsEpithelial differentiationWnt signalingRe-epithelializationWound healing |
| spellingShingle | Yongzheng Li Lingling Dong Yani Chen Wenjin Cai Guoli Yang Ying Wang Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing Stem Cell Research & Therapy Gingival mesenchymal stem cells Epithelial differentiation Wnt signaling Re-epithelialization Wound healing |
| title | Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing |
| title_full | Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing |
| title_fullStr | Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing |
| title_full_unstemmed | Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing |
| title_short | Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing |
| title_sort | epithelial differentiation of gingival mesenchymal stem cells enhances re epithelialization for full thickness cutaneous wound healing |
| topic | Gingival mesenchymal stem cells Epithelial differentiation Wnt signaling Re-epithelialization Wound healing |
| url | https://doi.org/10.1186/s13287-024-04081-9 |
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