期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 10, 期 5, 页码 711-724出版社
OXFORD UNIV PRESS
DOI: 10.1002/sctm.20-0289
关键词
bone marrow (BM); human mesenchymal stromal cells (MSCs); interleukin-10 (IL-10); peripheral B lymphocytes; placenta; regulatory B cells (Bregs); tissue specificity
资金
- NHRI [10A1-CSGP01-048, 10A1-CSPP06-014]
In vitro, placental MSCs significantly inhibit proliferation and differentiation of stimulated human peripheral B cell populations, while BM-MSCs do not. Additionally, P-MSCs increase all subsets of regulatory B cells (Bregs) producing IL-10, while BM-MSCs do not.
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.
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