人骨髓间充质干细胞对间质性肺纤维化抗损伤治疗研究

目的 研究骨髓间充质干细胞在间质性肺纤维化中的抗损伤治疗作用机制.方法 通过体外诱导的自然杀伤T细咆(NKT细胞)模拟间质性肺纤维化炎症损伤特点.以干扰素γ(IFN-γ),CD3,白介素2刺激培养外周血单个核细胞,得到含高比例CD3+ CD56+ NKT细胞,将这种培养的CD3+ CD56+ NKT细胞与人骨髓间充质干...

Anti-injury effects of human bone marrow mesenchymal stem cells on interstitial pulmonary fibrosis

Objective To explore the mechanism of anti-injury effects of human bone marrow mesenchymal stem cells on interstitial pulmonary fibrosis. Methods Natural killer T cell (NKT cell) was induced in vitro to simulate the inflammatory characteristics of interstitial pulmonary fibrosis. Peripheral blood mononuclcar cells (PBMC) were cultured with addition of interferon-γ (IFN-γ),CD3 antibody and interleukin-2 to contain high proportion of CD3+ CD56+ NKT cell,which was collected and cultured with human bone marrow mesenchymal stem cells. The cultured supernatants were harvested and NKT phenotype was identified by flow cytometry. The levels of transforming growth factor-β1 (TGF-β1 ) and interferon-inducible protein-10 (IP-10) in supernatants were detected by enzyme linked immunosorbent assay. The levels of IFN-γ and tumor necrosis factor α (TNF-α) were detected by liquid chip technique. CD3+ CD56+ NKT cell was cultured with human bone marrow mesenchymal stem cells and then co-cultured with 16HBE for four hours. The cell survival counting of 16HBE was detected by CCK8 assay. Results Mesenchymal stem cells had immunomodulatory effects on T lymphocyte subsets including CD3+ CD56+ NKT cell,reduced CD3+ CD56+ NKT cell in peripheral blood monouclear cells,induced differentiation of regulatory T cell,and reduced the levels of IFN-γ,TNF-α and other inflammatory cytokines. After co-cultured with mesenchymal stem cells,CD3+ CD56+ NKT cell decreased from (20. 33±1. 05)%to (15.17±1.75)%( P ＜0. 05). Secreting high levels of TGF-β1 and IP-10 was an important molecular basis of immunomodulation of mesenchymal stem cells. Mesenchymal stem cells relieved NKT cell-mediated damage of lung epithelial cells. Conclusions Mesenchymal stem cells have immunomodulatory effects on T lymphocyte subsets including CD3+ CD56+ NKT cell,and play a protective role in killing lung epithelial cells mediated by NKT cell.