Bioscience Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
Int J Mol Sci. 2019 Aug 8;20(16):3876. doi: 10.3390/ijms20163876.
Radiation therapy is one of the most important treatment modalities for thoracic tumors. Despite significant advances in radiation techniques, radiation-induced lung injury (RILI) still occurs in up to 30% of patients undergoing thoracic radiotherapy, and therefore remains the main dose-limiting obstacle. RILI is a potentially lethal clinical complication of radiotherapy that has 2 main stages: an acute stage defined as radiation pneumonitis, and a late stage defined as radiation-induced lung fibrosis. Patients who develop lung fibrosis have a reduced quality of life with progressive and irreversible organ malfunction. Currently, the most effective intervention for the treatment of lung fibrosis is lung transplantation, but the lack of available lungs and transplantation-related complications severely limits the success of this procedure. Over the last few decades, advances have been reported in the use of mesenchymal stem cells (MSCs) for lung tissue repair and regeneration. MSCs not only replace damaged lung epithelial cells but also promote tissue repair through the secretion of anti-inflammatory and anti-fibrotic factors. Here, we present an overview of MSC-based therapy for radiation-induced lung fibrosis, focusing in particular on the molecular mechanisms involved and describing the most recent preclinical and clinical studies carried out in the field.
放射治疗是治疗胸部肿瘤的重要方法之一。尽管放射技术有了显著进步,但高达 30%的胸部放射治疗患者仍会发生放射性肺损伤(RILI),因此它仍然是主要的剂量限制障碍。RILI 是放射治疗的一种潜在致命的临床并发症,有 2 个主要阶段:急性阶段定义为放射性肺炎,晚期阶段定义为放射性肺纤维化。发生肺纤维化的患者生活质量降低,出现进行性和不可逆转的器官功能障碍。目前,肺纤维化治疗最有效的干预措施是肺移植,但供肺不足和移植相关并发症严重限制了该手术的成功。在过去几十年中,间充质干细胞(MSCs)在肺组织修复和再生中的应用取得了进展。MSCs 不仅可以替代受损的肺上皮细胞,还可以通过分泌抗炎和抗纤维化因子来促进组织修复。在这里,我们对基于 MSC 的放射性肺纤维化治疗进行了综述,特别关注所涉及的分子机制,并描述了该领域最近进行的临床前和临床研究。