Chinnapaka Somaiah, Yang Katherine S, Surucu Yusuf, Bengur Fuat B, Arellano José A, Tirmizi Zayaan, Malekzadeh Hamid, Epperly Michael W, Hou Wen, Greenberger Joel S, Rubin J Peter, Ejaz Asim
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
iScience. 2023 Aug 17;26(9):107660. doi: 10.1016/j.isci.2023.107660. eCollection 2023 Sep 15.
Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM's potential in treating chronic-stage fibrosis.
放射治疗可导致晚期放射性皮肤纤维化（RISF），引起运动受限、疼痛和器官功能障碍。本研究评估了脂肪来源的细胞外基质（Ad-ECM）作为RISF缓解剂的作用。接受照射的雌性C57BL/6J小鼠出现纤维化，单次局部注射Ad-ECM可减轻纤维化，改善肢体运动，减少上皮厚度和胶原沉积。Ad-ECM治疗导致促炎和纤维化基因表达降低，抗炎细胞因子上调，促进M2巨噬细胞极化。照射后的人成纤维细胞与Ad-ECM共培养可下调纤维化基因表达并增强骨髓细胞迁移。Ad-ECM治疗还增加了内皮细胞中白细胞介素（IL）-4、IL-5和IL-15的表达，刺激M2巨噬细胞极化并减轻RISF。预防性使用Ad-ECM显示出缓解效果。本研究表明Ad-ECM在治疗慢性期纤维化方面具有潜力。
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