Zhang Chunyang, Zhu Yan, Wang Ji, Hou Lisheng, Li Wei, An Huaijie
Respiratory Department of Navy General Hospital, Beijing 100048, China.
Respiratory Department of International Hospital of Zhejiang University, Hangzhou 310009, China.
Stem Cells Int. 2019 Feb 5;2019:2457082. doi: 10.1155/2019/2457082. eCollection 2019.
Less quantity of transplanted mesenchymal stem cells (MSCs) influences the therapeutic effects on radiation-induced lung injury (RILI). Previous studies have demonstrated that MSCs overexpressing Chemokine (C-X-C motif) receptor 4 (CXCR4) could increase the quantity of transplanted cells to local tissues. In the present study, we conducted overexpressing CXCR4 human umbilical cord mesenchymal stem cell (HUMSC) therapy for RILI. C57BL mice received single dose of thoracic irradiation with 13 Gy of X-rays and then were administered saline, control HUMSCs, or CXCR4-overexpressing HUMSCs via tail vein. Transfection with CXCR4 enhanced the quantity of transplanted HUMSCs in the radiation-induced injured lung tissues. CXCR4-overexpressing HUMSCs not only improved histopathological changes but also decreased the radiation-induced expression of SDF-1, TGF-1, -SMA, and collagen I and inhibited the radiation-induced decreased expression of E-cadherin. Transplanted CXCR4-overexpressing HUMSCs also could express pro-SP-C, indicated adopting the feature of ATII. These finding suggests that CXCR4-overexpressing HUMSCs enhance the protection against RILI and may be a promising strategy for RILI treatment.
较少数量的移植间充质干细胞(MSCs)会影响对放射性肺损伤(RILI)的治疗效果。先前的研究表明,过表达趋化因子(C-X-C基序)受体4(CXCR4)的MSCs可增加移植到局部组织中的细胞数量。在本研究中,我们对RILI进行了过表达CXCR4的人脐带间充质干细胞(HUMSC)治疗。C57BL小鼠接受13 Gy X射线单次胸部照射,然后通过尾静脉给予生理盐水、对照HUMSCs或过表达CXCR4的HUMSCs。CXCR4转染增加了移植到放射性损伤肺组织中的HUMSCs数量。过表达CXCR4的HUMSCs不仅改善了组织病理学变化,还降低了辐射诱导的SDF-1、TGF-1、α-SMA和胶原蛋白I的表达,并抑制了辐射诱导的E-钙黏蛋白表达降低。移植的过表达CXCR4的HUMSCs也可表达前表面活性蛋白C,表明具有II型肺泡上皮细胞(ATII)的特征。这些发现表明,过表达CXCR4的HUMSCs增强了对RILI的保护作用,可能是一种有前景的RILI治疗策略。