title: 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.
authors.affiliation: Department of Pediatrics, Shengli Oil field Central Hospital, 31 Jinan Road, Dongying, Shandong, China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, the Affiliated Hospital of Medical College of Qingdao University, 1 Jiaozhou Road, Qingdao, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Shengli Oil field Central Hospital, 31 Jinan Road, Dongying, Shandong, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Shengli Oil field Central Hospital, 31 Jinan Road, Dongying, Shandong, China.
authors.forename: Xinhao
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Pediatrics, Shengli Oil field Central Hospital, 31 Jinan Road, Dongying, Shandong, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, Shengli Oil field Central Hospital, 31 Jinan Road, Dongying, Shandong, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Shengli Oil field Central Hospital, 31 Jinan Road, Dongying, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Ju
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000067290:Behavior Rating Scale; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000276:immunology / Q000628:therapy*; D002534:Hypoxia, Brain / Q000276:immunology / Q000628:therapy*; D007165:Immunosuppression Therapy; D007223:Infant; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D007511:Ischemia / Q000276:immunology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D000066829:Neuroprotection; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat