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

Abstract

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/10 µl 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.