期刊
PEDIATRIC BLOOD & CANCER
卷 65, 期 9, 页码 -出版社
WILEY
DOI: 10.1002/pbc.27247
关键词
apoptosis; immunosuppression; mesenchymal stem cells; severe aplastic anemia
资金
- China Medical University Hospital [DMR-107-051]
- Ministry of Science and Technology [MOST105-2314-B-040-017]
- Taiwan Ministry of Health and Welfare [MOHW107-TDU-B-212-123004]
BackgroundAlthough immune-mediated pathogenesis is considered an important aspect of severe aplastic anemia (SAA), its underlying mechanisms remain unclear. Mesenchymal stem cells (MSCs) are essential to the formation of specialized microenvironments in the bone marrow (BM), and MSC insufficiency can trigger the development of SAA. MethodsTo find MSC alterations in the SAA BM, we compared BM MSCs from five children with SAA and five controls. Peripheral blood mononuclear cells (PBMCs) were cocultured with MSCs to evaluate the supportive effects of MSCs on hematopoiesis. Cytometric bead array immunoassay was used to determine cytokine excretion by MSCs. The immune functions of MSCs and their conditioned medium (CM) were evaluated by PBMC proliferation assays. ResultsSAA MSCs were characterized by a high percentage of cells in the abnormal sub-G1 phase of the cell cycle, which suggests an increased rate of apoptosis in SAA MSCs. In comparison with control MSCs, PBMCs cocultured with SAA MSCs displayed significantly reduced PBMC proliferation (P=0.009). Aberrant cytokine profiles were secreted by SAA MSCs, with increased concentrations of interleukin-6, interferon-, tumor necrosis factor-, and interleukin-1 in the CM. PBMC proliferation assays demonstrated additional immunosuppressive effects of SAA MSCs (P=0.016) and their CM (P=0.013). ConclusionsOur data revealed increased apoptosis and PBMC suppression of SAA MSCs. The alterations of MSCs may contribute to the formation of functionally abnormal microenvironments in SAA BM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据