Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice
Abstract Background Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individua...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-023-03627-7 |
| _version_ | 1797355897424445440 |
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| author | Hamid Malekzadeh Yusuf Surucu Somaiah Chinnapaka Katherine S. Yang José A. Arellano Yasamin Samadi Michael W. Epperly Joel S. Greenberger J. Peter Rubin Asim Ejaz |
| author_facet | Hamid Malekzadeh Yusuf Surucu Somaiah Chinnapaka Katherine S. Yang José A. Arellano Yasamin Samadi Michael W. Epperly Joel S. Greenberger J. Peter Rubin Asim Ejaz |
| author_sort | Hamid Malekzadeh |
| collection | DOAJ |
| description | Abstract Background Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. Methods Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. Results Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. Conclusions Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis. |
| first_indexed | 2024-03-08T14:18:46Z |
| format | Article |
| id | doaj.art-08ddaa86957c42e5ab451a54ed4645ec |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-08T14:18:46Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-08ddaa86957c42e5ab451a54ed4645ec2024-01-14T12:13:47ZengBMCStem Cell Research & Therapy1757-65122024-01-0115111710.1186/s13287-023-03627-7Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in miceHamid Malekzadeh0Yusuf Surucu1Somaiah Chinnapaka2Katherine S. Yang3José A. Arellano4Yasamin Samadi5Michael W. Epperly6Joel S. Greenberger7J. Peter Rubin8Asim Ejaz9Department of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Radiation Oncology, University of Pittsburgh Cancer InstituteDepartment of Radiation Oncology, University of Pittsburgh Cancer InstituteDepartment of Plastic Surgery, University of Pittsburgh Medical CenterDepartment of Plastic Surgery, University of Pittsburgh Medical CenterAbstract Background Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. Methods Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. Results Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. Conclusions Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.https://doi.org/10.1186/s13287-023-03627-7RadiationFibrosisMetforminProphylactic therapyAdipose stem cells |
| spellingShingle | Hamid Malekzadeh Yusuf Surucu Somaiah Chinnapaka Katherine S. Yang José A. Arellano Yasamin Samadi Michael W. Epperly Joel S. Greenberger J. Peter Rubin Asim Ejaz Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice Stem Cell Research & Therapy Radiation Fibrosis Metformin Prophylactic therapy Adipose stem cells |
| title | Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice |
| title_full | Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice |
| title_fullStr | Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice |
| title_full_unstemmed | Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice |
| title_short | Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice |
| title_sort | metformin and adipose derived stem cell combination therapy alleviates radiation induced skin fibrosis in mice |
| topic | Radiation Fibrosis Metformin Prophylactic therapy Adipose stem cells |
| url | https://doi.org/10.1186/s13287-023-03627-7 |
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