Effects and mechanisms of human umbilical cord mesenchymal stem cells in ameliorating long-term radiation-induced lung injury
ZHENG Bo
LI Jiangyi
GUO Ling
ZHOU Yan
LÜ Yaoyao
ZHOU Guiqiang
QIN Tongzhou
LIU Liyuan
ZHANG Wei
DING Guirong
Abstract：Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cells(hUC-MSCs)on the long-term effects of radiation-induced lung injury(RILI)in mice induced by total body irradiation(TBI).Methods A total of 120 C57BL/6 mice were randomly divided into a control group(Ctrl group),an irradiation group(Rad group),and an irradiation+stem cell treatment group(Rad+MSCs group).Mice in the Rad group and the Rad+MSCs group received 6 Gy of 60 Co γ-ray TBI.Immediately after irradiation,the Rad+MSCs group was injected with an hUC-MSCs suspension(1×106/100 μL)via the tail vein.The homing of hUC-MSCs in the lungs was detected.The respiratory function,lung imaging,and pathological changes were evaluated at 4,12,and 20 weeks post-irradiation.The protein expressions of E-cadherin,Vimentin,α-SMA,and Egr1 in lung tissue were measured.Differentially expressed genes were screened and validated through transcriptomic analysis.Results The hUC-MSCs intervention significantly improved the 30-day survival rate post-irradiation.Respiratory function abnormalities were observed in the Rad group at 4 weeks post-irradiation,which progressively worsened over time and manifested as typical restrictive ventilatory dysfunction by 20 weeks.The hUC-MSCs intervention alleviated respiratory function impairment,with the most significant effect observed at 20 weeks.Pathological results showed that in the Rad group at 4 weeks post-irradiation,the lung tissue exhibited hyperemia and alveolar septal thickening;at 12 weeks,alveolar septal destruction was observed;and at 20 weeks,the tissue structure was loose with severe alveolar wall damage.The hUC-MSCs intervention ameliorated the pathological changes at all time points.At 20 weeks post-irradiation,the Rad group showed extensive ground-glass opacities,significantly increased collagen fiber deposition,downregulated E-cadherin expression,and upregulated Vimentin and α-SMA expression.Following hUC-MSCs intervention,these changes were mitigated,with epithelial markers rebounding and mesenchymal markers decreasing.Transcriptomic analysis identified 8 commonly differentially expressed genes,among which Egr1 expression exhibited dynamic changes:it was highly expressed in the Rad group at 4 weeks post-irradiation,but lowly expressed at 12 and 20 weeks.The hUC-MSCs intervention exerted a regulatory effect on Egr1 expression.Conclusion hUC-MSCs may improve the long-term effects of TBI-induced RILI by regulating the expression of Egr1 at different stages of RILI and by modulating the epithelial-mesenchymal transition process in the intermediate to late phases.
Keywords：human umbilical cord mesenchymal stem cellsmouseionizing radiationradiation-induced pulmonary fibrosisradiation-induced lung injuryepithelial-mesenchymal transitionstem cell transplantationrespiratory function
Publication Date：2026-05-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：10( 641-650 )