Alleviation of radiation lung damage by administration of gene-modified mesenchymal stem cells.

e13568 Background: Radiation pneumonitis (RP) and subsequent radiation pulmonary fibrosis (RPF) is a common and serious complication in the treatment with radiation therapy (RT) for lung cancer. In order to investigate the alleviation efficacy by gene-modified mesenchymal stem cells (MSCs), we assessed whether adenovirus-transduced MSCs with the soluble transforming growth factor-beta type II receptor (Ad-sTβR) could reduce RP and RFP. Methods: MSCs from male C57BL/6 mice were isolated and verified. The whole lung of each female C57BL/6 mouse was irradiated with a single dose of 14Gy. Injection of PBS, Ad-sTβR, MSCs, and Ad-sTβR-transduced MSCs (Ad-sTβR-MSCs) by tail vein were administrated immediately and 14 days after radiation, respectively. RP and RPF were assessed by H&E, Masson trichrome staining, MDA, hydroxyproline and TGF-β1 assay as well as quantitative RT-PCR and Western Blot for CTGF and α-SMA. Furthermore, the differentiation assays of male MSCs into type II pneumocytes were performed by Real-time PCR and FISH for Y chromosome. Results: The homing effect of MSCs to irradiated murine lung was detected by Real-time PCR for Y chromosome on day 30. By comparison with groups of RT+PBS, RT+MSCs and RT+Ad-sTβR, there was a significant reduction for lung injury in the group of Ad-sTβR-MSCs on day 120, which was demonstrated not only by staining of H&E and Masson trichrome, but also by assay of MDA, hydroxyproline and plasma active TGF-β1. Administration of Ad-sTβR-MSCs significantly decreased the relative mRNA and protein levels of CTGF and α-SMA. In addition, it was observed by real-time PCR for Y chromosome that about 11% type II pneumocytes were derived from donor male MSCs, which was further confirmed by FISH. Conclusions: These findings suggested that MSCs can home to injured lung, and the strategy of Ad-sTβR gene-modified MSCs could potential alleviate RP as well as RPF by differentiation of engrafted MSCs into type II pneumocytes. No significant financial relationships to disclose.