Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes
Abstract Background Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-022-03127-0 |
| _version_ | 1811238931647168512 |
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| author | Jing Wang Junrong Cai Qian Zhang Jiaqing Wen Yunjun Liao Feng Lu |
| author_facet | Jing Wang Junrong Cai Qian Zhang Jiaqing Wen Yunjun Liao Feng Lu |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Abstract Background Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis. Methods Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co‐culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes. Results Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization. Conclusion Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation. |
| first_indexed | 2024-04-12T12:50:57Z |
| format | Article |
| id | doaj.art-d5066418c1a74803bfca164d6e006c14 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-12T12:50:57Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-d5066418c1a74803bfca164d6e006c142022-12-22T03:32:29ZengBMCStem Cell Research & Therapy1757-65122022-10-0113111310.1186/s13287-022-03127-0Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytesJing Wang0Junrong Cai1Qian Zhang2Jiaqing Wen3Yunjun Liao4Feng Lu5Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityAbstract Background Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis. Methods Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co‐culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes. Results Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization. Conclusion Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation.https://doi.org/10.1186/s13287-022-03127-0SclerodermaFat graftingAdipocyteDedifferentiated adipocyteAdipose-derived stem cell |
| spellingShingle | Jing Wang Junrong Cai Qian Zhang Jiaqing Wen Yunjun Liao Feng Lu Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes Stem Cell Research & Therapy Scleroderma Fat grafting Adipocyte Dedifferentiated adipocyte Adipose-derived stem cell |
| title | Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes |
| title_full | Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes |
| title_fullStr | Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes |
| title_full_unstemmed | Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes |
| title_short | Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes |
| title_sort | fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes |
| topic | Scleroderma Fat grafting Adipocyte Dedifferentiated adipocyte Adipose-derived stem cell |
| url | https://doi.org/10.1186/s13287-022-03127-0 |
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