國家衛生研究院 NHRI:Item 3990099045/13170
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    题名: Resident vs nonresident multipotent mesenchymal stromal cell interactions with B lymphocytes result in disparate outcomes
    作者: Lee, W;Wang, LT;Yen, ML;Hsu, PJ;Lee, YW;Liu, KJ;Lin, KI;Su, YW;Sytwu, HK;Yen, BL
    贡献者: Institute of Cellular and Systems Medicine;National Institute of Cancer Research;Immunology Research Center;National Institute of Infectious Diseases and Vaccinology
    摘要: Multipotent human mesenchymal stromal cells (MSCs) from multiple organs including the bone marrow (BM) and placenta harbor clinically relevant immunomodulation best demonstrated toward T lymphocytes. Surprisingly, there is limited knowledge on interactions with B lymphocytes, which originate from the BM where there is a resident MSC. With increasing data demonstrating MSC tissue-specific propensities impacting therapeutic outcome, we therefore investigated the interactions of BM-MSCs—its resident and “niche” MSC—and placental MSCs (P-MSCs), another source of MSCs with well-characterized immunomodulatory properties, on the global functional outcomes of pan-peripheral B cell populations. We found that P-MSCs but not BM-MSCs significantly inhibit proliferation and further differentiation of stimulated human peripheral B populations in vitro. Moreover, although BM-MSCs preserve multiple IL-10-producing regulatory B cell (Breg) subsets, P-MSCs significantly increase all subsets. To corroborate these in vitro findings in vivo, we used a mouse model of B-cell activation and found that adoptive transfer of P-MSCs but not BM-MSCs significantly decreased activated B220+ B cells. Moreover, adoptive transfer of P-MSCs but not BM-MSCs significantly decreased the overall B220+ B-cell proliferation and further differentiation, similar to the in vitro findings. P-MSCs also increased two populations of IL-10-producing murine Bregs more strongly than BM-MSCs. Transcriptome analyses demonstrated multifactorial differences between BM- and P-MSCs in the profile of relevant factors involved in B lymphocyte proliferation and differentiation. Our results highlight the divergent outcomes of tissue-specific MSCs interactions with peripheral B cells, and demonstrate the importance of understanding tissue-specific differences to achieve more efficacious outcome with MSC therapy.
    日期: 2021-05
    關聯: Stem Cells Translational Medicine. 2021 May;10(5):711-724.
    Link to: http://dx.doi.org/10.1002/sctm.20-0289
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2157-6564&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000612358900001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85099796030
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