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| Role of umbilical cord mesenchymal stem cell transplantation in alleviating alveolar cell senescence |
| ZHAO Wenyue, LI Na, LI Kejun, DU Liqing, LIU Qiang |
| Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192 China |
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Abstract Objective To investigate whether the transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) can alleviate radiation-induced pulmonary fibrosis (RIPF) and attenuate intrapulmonary cellular senescence in mice with RIPF. Methods The C57BL/6 mice were unilaterally irradiated with 17 Gy in the right lung to construct RIPF models. UC-MSCs were injected into the caudal vein at 3 months after radiation, and samples were taken at 6 months. The survival rate of mice was recorded, and the lung organ ratio was calculated. Lung structure and collagen deposition were observed by hematoxylin-eosin staining and Masson staining. The expression of senescence secretion-associated phenotype (SASP) was measured by quantitative real-time polymerase chain reaction. Intrapulmonary cellular senescence was assessed by β-Gal immunohistochemistry. The expression of key proteins in the P53-P21 and P16 pathways was measured by Western blot. P21 expression in the lung was measured by tissue immunofluorescence. Results Compared with the untreated group, RIPF mice treated with UC-MSCs showed an improved survivalrate, reduced collagen deposition, and an improvement incollapse and thickening of alveolar structure. Increased β-Gal-positive senescent cells and high expression of SASP (IL-6, IL-8, IL-1β) in the lung of RIPF mice were all reduced after UC-MSC treatment. The abnormally increased levels of P53, p-P53, P21 and P16 proteins in RIPF mice were reduced by UC-MSC treatment. Conclusion UC-MSCs may reduce cellular senescence in fibrotic lungs and alleviate RIPF by inhibiting P53-P21 and P16 pathways, which is expected to be used for the treatment of radiation-induced lung injury.
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Received: 28 November 2021
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