Riccobono Diane, Nikovics Krisztina, François Sabine, Favier Anne-Laure, Jullien Nicolas, Schrock Gerrit, Scherthan Harry, Drouet Michel
Institut de Recherche Biomédicale des Armées (IRBA), Unité de Radiobiologie, Brétigny sur Orge Cedex, France.
Institut de Recherche Biomédicale des Armées (IRBA), Département des Services, Unité Imagerie, Brétigny sur Orge Cedex, France.
Health Phys. 2018 Jul;115(1):37-48. doi: 10.1097/HP.0000000000000822.
The cutaneous radiation syndrome is the clinical consequence of local high-dose irradiation. It is characterized by extensive inflammation, necrosis, and poor revascularization of the skin, resulting in muscle inflammation and fibrosis. Based on these physiopathological processes, subcutaneous injections of adipose-tissue-derived stem/stromal cells have shown favorable effects on skin-wound healing in a minipig model of cutaneous radiation syndrome, in which muscle fibrosis persisted. Since fibrosis is mainly due to the inflammatory processes that often affect underlying tissues as well, the beneficial effects of intramuscular injections of adipose-tissue-derived stem/stromal cells on tissue recovery were evaluated. The polarization of the inflammatory response of irradiated muscle in a minipig model of cutaneous radiation syndrome was determined after acute local irradiation with 50 Gy gamma rays in a preliminary study (six minipigs). Analysis of the main inflammatory cytokines of the inflammatory response M1 (IL-1-beta and IL-6) and M2 (IL-10 and TGF-beta) by western blotting and in situ hybridization, as well as analysis of CD80/CD206 M1/M2 macrophage-specific markers by immunohistochemistry on minipig muscle samples, was performed 76 d after irradiation. The treatment of irradiated muscles with autologous adipose-tissue-derived stem/stromal cells led to an increase in IL-10 and TGF-beta, being associated with an increase in CD68+/CD206+ cells in this area. This highlights a polarization of M2 in the inflammatory response and indicates that adipose-tissue-derived stem/stromal cells may direct the irradiated tissues' inflammatory response towards a proregenerative outcome.
皮肤辐射综合征是局部高剂量照射的临床后果。其特征是皮肤广泛炎症、坏死和血管再生不良，导致肌肉炎症和纤维化。基于这些病理生理过程，在皮肤辐射综合征小型猪模型中，皮下注射脂肪组织来源的干细胞/基质细胞对皮肤伤口愈合显示出良好效果，该模型中肌肉纤维化持续存在。由于纤维化主要是由通常也会影响深层组织的炎症过程引起的，因此评估了肌肉注射脂肪组织来源的干细胞/基质细胞对组织恢复的有益作用。在一项初步研究（六只小型猪）中，用50 Gyγ射线进行急性局部照射后，确定了皮肤辐射综合征小型猪模型中受照射肌肉炎症反应的极化情况。在照射后76天，通过蛋白质印迹法和原位杂交分析炎症反应的主要炎症细胞因子M1（IL-1-β和IL-6）和M2（IL-10和TGF-β），并通过免疫组织化学对小型猪肌肉样本分析CD80/CD206 M1/M2巨噬细胞特异性标志物。用自体脂肪组织来源的干细胞/基质细胞治疗受照射的肌肉导致IL-10和TGF-β增加，这与该区域CD68+/CD206+细胞的增加有关。这突出了炎症反应中M2的极化，并表明脂肪组织来源的干细胞/基质细胞可能将受照射组织的炎症反应导向促进再生的结果。
