The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease
Abstract Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs, leading to significant morbidity and reduced quality of life. Despite ongoing research, the underlying pathogenesis of SSc remains unclear, and treatment options ar...
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BMC
2025-07-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04470-8 |
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| author | Ziyu Wang Mengqi Shi Zonghao Liu Yahui Chen Xiangguang Shi Jiucun Wang |
| author_facet | Ziyu Wang Mengqi Shi Zonghao Liu Yahui Chen Xiangguang Shi Jiucun Wang |
| author_sort | Ziyu Wang |
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| description | Abstract Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs, leading to significant morbidity and reduced quality of life. Despite ongoing research, the underlying pathogenesis of SSc remains unclear, and treatment options are limited. Stromal vascular fraction (SVF), a naturally occurring cell population that includes mesenchymal stem cells (MSCs), has emerged as a potential therapeutic agent for various fibrotic diseases. This study aimed to investigate the therapeutic effects and underlying mechanisms of SVF in a bleomycin-induced mouse model of skin fibrosis. Methods SVF was isolated from the inguinal adipose tissue of C57BL/6 mice and administered subcutaneously or intradermally at different disease stages to assess its impact on skin fibrosis. Histological analyses were performed to evaluate dermal thickness and collagen deposition. In vivo imaging and immunofluorescence were used to track the retention of SVF within fibrotic tissue over time, particularly in the subcutaneous layer. Flow cytometry and immunofluorescence were employed to examine cutaneous vascular pathology and the secretion of antifibrotic factors, such as hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF-2). Finally, we investigated the contribution of major SVF subsets to cutaneous fibrosis and the mechanisms by which these subsets mediate therapeutic effects. Results SVF significantly attenuated skin fibrosis in both early and late stages of disease, as evidenced by reduced dermal thickness and collagen deposition. Notably, SVF showed prolonged retention in fibrotic tissues—especially in the subcutaneous layer—for at least 18 days post-injection, with antifibrotic effects primarily mediated through paracrine mechanisms. In early-stage fibrosis, SVF inhibited endothelial–mesenchymal transition and mitigated skin vascular damage. In late-stage fibrosis, SVF continued to secrete antifibrotic factors, including HGF and FGF-2. Subsequent analyses identified the CD45-negative subset of SVF as a key regulator of skin fibrosis. Conclusion SVF, particularly its CD45-negative subset, holds considerable promise for the treatment of SSc-associated skin fibrosis. These findings suggest that SVF-based therapies could be effective in managing fibrosis-related diseases and offer valuable insights for future clinical applications. |
| format | Article |
| id | doaj-art-7afd558a5a684a90a846553804323825 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-7afd558a5a684a90a8465538043238252025-08-20T04:01:25ZengBMCStem Cell Research & Therapy1757-65122025-07-0116111510.1186/s13287-025-04470-8The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of diseaseZiyu Wang0Mengqi Shi1Zonghao Liu2Yahui Chen3Xiangguang Shi4Jiucun Wang5State Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan UniversityState Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan UniversityState Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan UniversityState Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan UniversityDepartment of Dermatology, Huashan Hospital, Fudan UniversityState Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan UniversityAbstract Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs, leading to significant morbidity and reduced quality of life. Despite ongoing research, the underlying pathogenesis of SSc remains unclear, and treatment options are limited. Stromal vascular fraction (SVF), a naturally occurring cell population that includes mesenchymal stem cells (MSCs), has emerged as a potential therapeutic agent for various fibrotic diseases. This study aimed to investigate the therapeutic effects and underlying mechanisms of SVF in a bleomycin-induced mouse model of skin fibrosis. Methods SVF was isolated from the inguinal adipose tissue of C57BL/6 mice and administered subcutaneously or intradermally at different disease stages to assess its impact on skin fibrosis. Histological analyses were performed to evaluate dermal thickness and collagen deposition. In vivo imaging and immunofluorescence were used to track the retention of SVF within fibrotic tissue over time, particularly in the subcutaneous layer. Flow cytometry and immunofluorescence were employed to examine cutaneous vascular pathology and the secretion of antifibrotic factors, such as hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF-2). Finally, we investigated the contribution of major SVF subsets to cutaneous fibrosis and the mechanisms by which these subsets mediate therapeutic effects. Results SVF significantly attenuated skin fibrosis in both early and late stages of disease, as evidenced by reduced dermal thickness and collagen deposition. Notably, SVF showed prolonged retention in fibrotic tissues—especially in the subcutaneous layer—for at least 18 days post-injection, with antifibrotic effects primarily mediated through paracrine mechanisms. In early-stage fibrosis, SVF inhibited endothelial–mesenchymal transition and mitigated skin vascular damage. In late-stage fibrosis, SVF continued to secrete antifibrotic factors, including HGF and FGF-2. Subsequent analyses identified the CD45-negative subset of SVF as a key regulator of skin fibrosis. Conclusion SVF, particularly its CD45-negative subset, holds considerable promise for the treatment of SSc-associated skin fibrosis. These findings suggest that SVF-based therapies could be effective in managing fibrosis-related diseases and offer valuable insights for future clinical applications.https://doi.org/10.1186/s13287-025-04470-8Systemic sclerosisStromal vascular fractionSkin fibrosisBleomycin-induced skin fibrosis |
| spellingShingle | Ziyu Wang Mengqi Shi Zonghao Liu Yahui Chen Xiangguang Shi Jiucun Wang The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease Stem Cell Research & Therapy Systemic sclerosis Stromal vascular fraction Skin fibrosis Bleomycin-induced skin fibrosis |
| title | The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease |
| title_full | The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease |
| title_fullStr | The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease |
| title_full_unstemmed | The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease |
| title_short | The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease |
| title_sort | stromal vascular fraction mitigates bleomycin induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease |
| topic | Systemic sclerosis Stromal vascular fraction Skin fibrosis Bleomycin-induced skin fibrosis |
| url | https://doi.org/10.1186/s13287-025-04470-8 |
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