Jiang Xinping, Jiang Xin, Qu Chao, Chang Pengyu, Zhang Chu, Qu Yaqin, Liu Yongjun
Department of Oncological Radiotherapy, The First Bethune Hospital of Jilin University, Changchun, China.
Department of Oncological Radiotherapy, The Second Bethune Hospital of Jilin University, Changchun, China.
Cytotherapy. 2015 May;17(5):560-70. doi: 10.1016/j.jcyt.2015.02.011. Epub 2015 Mar 17.
Radiation-induced lung injury (RILI) commonly occurs in patients with thoracic cancer. However, an effective treatment option has not yet been established. Adipose-derived mesenchymal stromal cells (Ad-MSCs) have significant potential for clinical use, but their role in RILI is currently unknown. We aimed to evaluate the therapeutic capacity of Ad-MSCs to heal acute RILI in rats.
Sprague-Dawley rats were used in this study. Rat Ad-MSCs were delivered through the tail veins of rats 2 h after thorax irradiation. Lung histopathologic findings, pulmonary levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10 and tumor necrosis factor-α), pro-fibrotic factors (transforming growth factor [TGF]-β1, connective tissue growth factor, α-smooth muscle actin and type 1 collagen), pro- or anti-apoptotic mediators (Bcl-2, Bax and caspase-3) and the multifunctional factor hepatocyte growth factor were evaluated after Ad-MSC transplant.
Intravenous delivery of Ad-MSCs attenuated acute RILI. Further studies showed that Ad-MSCs had anti-inflammation and anti-fibrotic effects and maintained lung epithelium integrity, as indicated by reduced serum levels of the pro-inflammatory cytokines IL-1, IL-6 and tumor necrosis factor-α, increased levels of the anti-inflammatory cytokine IL-10, and downregulated transforming growth factor -β1, α-smooth muscle actin and type 1 collagen levels in irradiated lung tissues. Ad-MSCs also regulated the expression of pro- and anti-apoptotic mediators (Bcl-2, Bax and caspase-3) to protect lung cells from apoptosis.
Intravenous Ad-MSC delivery attenuated acute RILI through anti-inflammation, anti-fibrosis and anti-apoptosis mechanisms.
放射性肺损伤（RILI）常见于胸段肿瘤患者。然而，尚未确立有效的治疗方案。脂肪来源的间充质基质细胞（Ad-MSCs）具有显著的临床应用潜力，但其在RILI中的作用目前尚不清楚。我们旨在评估Ad-MSCs对大鼠急性RILI的治疗能力。
本研究使用Sprague-Dawley大鼠。在胸部照射后2小时，通过大鼠尾静脉注射大鼠Ad-MSCs。在Ad-MSCs移植后，评估肺组织病理学结果、肺组织中炎性细胞因子（白细胞介素[IL]-1、IL-6、IL-10和肿瘤坏死因子-α）、促纤维化因子（转化生长因子[TGF]-β1、结缔组织生长因子、α平滑肌肌动蛋白和I型胶原）、促凋亡或抗凋亡介质（Bcl-2、Bax和半胱天冬酶-3）以及多功能因子肝细胞生长因子的水平。
静脉注射Ad-MSCs减轻了急性RILI。进一步研究表明，Ad-MSCs具有抗炎和抗纤维化作用，并维持肺上皮完整性，这表现为促炎细胞因子IL-1、IL-6和肿瘤坏死因子-α的血清水平降低、抗炎细胞因子IL-10水平升高，以及照射肺组织中转化生长因子-β1、α平滑肌肌动蛋白和I型胶原水平下调。Ad-MSCs还调节促凋亡和抗凋亡介质（Bcl-2、Bax和半胱天冬酶-3）的表达，以保护肺细胞免于凋亡。
静脉注射Ad-MSCs通过抗炎、抗纤维化和抗凋亡机制减轻急性RILI。
