The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2.

The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2.
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DOI:
10.1038/srep08713
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发表时间:
2015-03-04
期刊:
影响因子:
4.6
通讯作者:
Liu F
Liu F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dong LH;Jiang YY;Liu YJ;Cui S;Xia CC;Qu C;Jiang X;Qu YQ;Chang PY;Liu F

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放射性肺纤维化是一种常见病,由于肺内气体交换区的进行性破坏,预后较差。最近,一种应用间充质干细胞治疗肺纤维化的新策略已经取得了很高的治疗效果。在本研究中,我们试图使用人脂肪组织来源的间充质干细胞来预防接受半胸照射(15 Gy射线)的SD大鼠的疾病。为了研究间充质干细胞在改善放射性肺纤维化中的特殊作用,我们用人皮肤成纤维细胞或磷酸盐缓冲液处理对照组大鼠。骨髓间充质干细胞输注后,宿主分泌的肝细胞生长因子(HGF)和前列腺素E2(PGE2)较对照组升高。相反,输注间充质干细胞后,肿瘤坏死因子-α(α-β)和转化生长因子-β1(TGFR-β1)水平降低。因此,受照射的肺的结构被保存下来,没有明显的成纤维细胞激活或损伤部位的胶原沉积。此外,间充质干细胞能够阻止照射后的肺泡II型上皮细胞发生上皮-间充质转化。总的来说,这些数据证实了间充质干细胞在暴露于电离辐射后具有限制肺纤维化的潜力。
Radiation-induced pulmonary fibrosis is a common disease and has a poor prognosis owing to the progressive breakdown of gas exchange regions in the lung. Recently, a novel strategy of administering mesenchymal stem cells for pulmonary fibrosis has achieved high therapeutic efficacy. In the present study, we attempted to use human adipose tissue-derived mesenchymal stem cells to prevent disease in Sprague-Dawley rats that received semi-thoracic irradiation (15 Gy). To investigate the specific roles of mesenchymal stem cells in ameliorating radiation-induced pulmonary fibrosis, we treated control groups of irradiated rats with human skin fibroblasts or phosphate-buffered saline. After mesenchymal stem cells were infused, host secretions of hepatocyte growth factor (HGF) and prostaglandin E2 (PGE2) were elevated compared with those of the controls. In contrast, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta1 (TGF-β1) levels were decreased after infusion of mesenchymal stem cells. Consequently, the architecture of the irradiated lungs was preserved without marked activation of fibroblasts or collagen deposition within the injured sites. Moreover, mesenchymal stem cells were able to prevent the irradiated type II alveolar epithelial cells from undergoing epithelial-mesenchymal transition. Collectively, these data confirmed that mesenchymal stem cells have the potential to limit pulmonary fibrosis after exposure to ionising irradiation.
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