國家衛生研究院 NHRI:Item 3990099045/7640
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    题名: Differential modulation of TH17 responses by human mesenchymal stem cells: Role of paracrine factors vs cell-cell contact
    作者: Wang, WB;Wei, CF
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Background: Recent advances in stem cell research have generated much hope for regenerative medicine, and multilineage mesenchymal stem cells (MSCs) are a highly popular source of stem cells used in clinical trials, since these versatile somatic progenitors also possess strong immunosuppressive properties by suppressing T helper (Th) 1 lymphocyte responses – shifting towards a Th2 response – while enhancing regulatory T lymphocyte numbers. Very recently, focus has turned to investigating whether MSCs can affect Th17 lymphocytes, a population of strongly inflammatory and pathogenic T cells highly associated with autoimmune disorders. While initial reports demonstrate that MSCs suppress Th17 responses, newer published data surprisingly show that MSCs can also promote Th17 responses. We therefore sought to clarify these conflicting outcomes: to elucidate the regulation of Th17 cells by MSCs and the mechanisms involved. Methods: We took advantages of easily ex vivo -expanded human placenta-derived multipotent cells (PDMCs) – a population of MSCs which are ethically unproblematic and clinically relevant – which our lab has isolated and well-characterized for multipotency and immunomodulatory properties. Results: We found that in vitro and ex vivo co-culture of human allogeneic peripheral blood leukocytes (PBLs) or CD4-selected lymphocytes (CD4-L) with these human MSCs significantly suppressed Th17 cell responses. However, this suppression was lost when cell contact between MSCs and PBLs or CD4-L was abrogated, a surprising result since suppression of Th1 responses in human MSC studies have been consistently shown to be mediated by secreted factors. Conclusion(s): Our discrepant findings strongly suggest that MSC-secreted factors and cell surface molecules play opposing roles with regards to allogeneic Th17 cells. This data is important in shedding light on the why not all types of autoimmune diseases are equally responsive to MSC therapy, especially given the critical role of Th17 in some of these diseases. Further research is underway to elucidate the detailed molecular mechanism of these complex MSC interactions with Th17 cells.
    日期: 2013-11
    關聯: Allergy. 2013 Nov;68(Suppl. S98):9.
    Link to: http://dx.doi.org/10.1111/all.12281
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0105-4538&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000325897100030
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