|Title:||Resident vs nonresident multipotent mesenchymal stromal cell interactions with B lymphocytes result in disparate outcomes||Authors:||Lee, Wei
Yen, B Linju
|Keywords:||bone marrow (BM); human mesenchymal stromal cells (MSCs); interleukin-10 (IL-10); peripheral B lymphocytes; placenta; regulatory B cells (Bregs); tissue specificity||Issue Date:||28-Jan-2021||Source:||Stem cells translational medicine||Abstract:||
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.
|Appears in Collections:||醫學系|
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