Therapeutic Effects Of Bone Marrow Mesenchymal Stem Cells On Radiation-induced Lung Injury

Background and objectiveThe radiation-induced lung injury commonly occurs after thoracicradiation therapy, which is a count limiting factor in radiationtherapy.The patient’s condition is progressive, debilitating and fatal withtypical lesions of interstitial pneumonitis and fibrosis in lung disease.Early clinical manifestations areirritating cough, chest congestion, andshortness of breath.Late manifestation mainly is refractorybreathlessness, which isirreversible. At present, there is no specialtreatment method for the lung injury. The relieving symptoms andsupporting therapy applied with antibiotics, hormone and oxygen havebecome the important therapeutic methods, which just can inhibite therelease of inflammatory factors, but there is no definite therapeutic effectfor the damaged cells.The mesenchymal stem cells (MSCs) had beenwidely used in treating rodent model of radiation-induced lung injury,which can achieve a satisfactory therapeutic effect. On this basis, weaimed at whether the therapeutic effects of bone marrow-derivedMSCs(BM-MSCs) on the radiation-induced lung injury was count-dependent.It has a certain significance for guiding clinical treatment.MethodsThe whole thorax inmice was received by single-dose radiationwith18Gy of X-rays.Then the mice were administrated with BM-MSCs intravenously through the tail within24h after irradiation, which dividedinto four groupsrandomly: the control (lung irradiation+phosphatebuffer solution), low count BM-MSCs (lung irradiation+1×103hBM-MSCs/g), middle count BM-MSCs (lung irradiation+5×103hBM-MSCs/g) and high count BM-MSCs (lung irradiation+1×104hBM-MSCs/g) groups. Thereafter, the death of mice in different groupswas observed in the experimental study, and lungs and serum werecollected at different time points for observing the change of histologyand detecting protein levels, which evaluated the factor expressionsrelated with inflammatory and fibrosis.Results⑴The radiation-induced lung injury was significantly reduced byBM-MSCs,which increased the survival rate of mice, to inhibit thefibrosis and immune regulation by the action of anti-inflammatory.⑵BM-MSCs can be differentiated into the function cells,such asalveolar epithelial cells and vascular endothelial cells in theradiation-induced lung injury.⑶Interestingly, we found that the low count BM-MSCs obviouslyreduced radiation-induced lung injury as compared with other groups,albeit the mortality was significantly higher in the high-count BM-MSCsgroup.(4)BM-MSCs in the radiation-induced lung injury could differentiate into alveolar epithelial cells and vascular endotheliocytes,which increased the expressions of HGF and IL-10, and decreased theexpressions of TNF-α, TGF-β1and ColⅢ.Conclusions⑴Transplantation of low-count BM-MSCs reduced significantlythe mortality, and promoted effectively the functional recovery ofradiation-induced lung injury.⑵The effect of radiation-induced lung injury treated withBM-MSCs was count-independent, transplant low count BM-MSCsshowed obviously both safe and repairing effects.⑶The BM-MSCs in the radiation-induced lung injury promote theregeneration and repairing in lung tissues. The BM-MSCs in repairingradiation-induced lung injury played a significant role in some relatedfactors secreted by paracrine.