Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice.
Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice.
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DOI：
10.1186/s13287-023-03627-7
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发表时间：
2024-01-08
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
放射治疗通常会导致晚期放射性皮肤纤维化(RISF)，导致运动障碍和不适。我们进行了一项全面的研究，以评估二甲双胍和脂肪干细胞(ASCs)，无论是自体或同种异体，单独或联合治疗，在缓解RISF方面的有效性。以C57BL/6J小鼠后肢照射模型为典型的RISF模型，我们在预防(照射后第1天开始)和治疗(照射后第14天开始，同时出现纤维化症状)两种情况下评价了二甲双胍、ASCs或它们的组合。我们测量肢体运动，检查皮肤组织学，并分析基因表达以评估治疗效果。预防性的二甲双胍和ASCs，无论是自体的还是同种异体的，都有效地防止了晚期纤维化，二甲双胍显示了令人振奋的结果。然而，当预防性使用时，联合治疗并没有提供额外的好处。事实证明，单独或与二甲双胍联合使用自体ASCs对晚期RISF最有效。在减轻放射性皮肤损伤方面，预防性干预的效果优于晚期治疗。共培养研究表明，ASCs和二甲双胍下调了小鼠和人成纤维细胞的炎症和纤维化基因表达。我们的研究表明，二甲双胍作为预防RISF的预防措施具有潜力，ASCs和二甲双胍的联合应用有望用于晚期RISF的治疗。这些发现对改善那些受辐射引起的皮肤纤维化影响的人的生活质量具有临床意义。网上版载有补充材料，可在10.1186/s13287-023-03627-7查阅。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s13287-023-03627-7.
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影响因子：
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作者：
Nogueira, Regiane Mazzarioli Pereira;Vital, Flavia Maria Ribeiro;Bernabe, Daniel Galera;Carvalho, Marcos Brasilino de
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