Transplantation of placenta-derived mesenchymal stem cells reduces hypoxic-ischemic brain damage in rats by ameliorating the inflammatory response

摘要

Hypoxic-ischemic brain damage(HIBD)is a common cause of infant death.The purpose of our research was to explore the immunoregulatory mechanism of placenta-derived mesenchymal stem cells(PD-MSCs)in HIBD treatment.Seven-day-old rat pups were randomly divided into HIBD,PD-MSC,fibroblast,and control groups.Forty-eight hours after HIBD induction,cells at a density of 5×104 cells/10µl were injected into the cerebral tissue in the PD-MSC and fibroblast groups.The TNF-α,interleukin-17(IL-17),interferon-γ(IFN-γ),and IL-10 levels were detected through quantitative real-time polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA).Regulatory T cell(Tregs)populations were detected through flow cytometry,and forkhead box P3(Foxp3)was measured through western blot analysis.Behavioral tests and gross and pathological examinations showed that PD-MSC treatment exerted significantly stronger neuroprotective effects than the other treatments.The expression levels of pro-inflammatory cytokines were substantially upregulated after HI injury.Compared with fibroblast treatment,PD-MSC treatment inhibited the production of pro-inflammatory cytokines and increased the production of IL-10 in the ischemic hemispheres and peripheral blood serum(all P<0.01).Flow cytometry results showed a notable increase in the number of Tregs within the spleen of the HIBD group.Moreover,the number of Tregs and the Foxp3 expression levels were higher in the PD-MSC treatment group than in the HIBD and fibroblast groups(all P<0.01).Our research suggests that the mechanism of PD-MSC treatment for HIBD partially involves inflammatory response suppression.