Resident vs nonresident multipotent mesenchymal stromal cell interactions with B lymphocytes result in disparate outcomes

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.

Advances in Mesenchymal Stem Cell Therapy for Immune and Inflammatory Diseases: Use of Cell-Free Products and Human pluripotent Stem Cell-Derived Mesenchymal Stem Cells

“…Interestingly, immunomodulatory paracrine factors such as PGE 2 and IDO inducible by inflammatory signals including IFN‐γ and IL‐1β are prominent in MSC interactions across leukocyte subpopulations including all lymphoid cells including T cells, NKs, 20 and B cells in which IL‐10‐expressing regulatory B cells are expanded 21,22 . Reports are most scarce for MSC‐B cell interactions, but most demonstrate suppression of B cell proliferation, differentiation, and antibody production 23‐29 ; our recent report found that MSC‐B cell interactions may be more complex than previously thought due to MSC source‐specific differences in expression of relevant factors 30 . Such information on tissue‐specific MSC properties may provide insights which could prove relevant for clinical application 11,31 …”

“…Close attention should be paid to trial results for psoriasis, also a predominately Th17 disease, which have been numerous recently. Another variable to follow closely is whether different sources of MSCs would be particularly suited to specific diseases, since preclinical results are starting to indicate tissue‐specific differences in MSC immunomodulatory mechanisms 30,48 …”

Placental mesenchymal stem cells boost M2 alveolar over M1 bone marrow macrophages via IL-1β inKlebsiella-mediated acute respiratory distress syndrome

“…Single-cell suspensions derived from lung lobes were stained with antibodies recognising CD45, CD11b, F4/80, CD206, inducible nitric oxide synthase (iNOS), arginase-1 (Arg1), TNF-α (all from eBioscience, San Diego, California, USA), or 2′,7′-dichlorofluorescein diacetate (DCFDA, Sigma-Aldrich, Missouri, USA) for 30 min according to manufacturer’s instructions, then assessed by flow cytometry or analysed with t-distributed stochastic neighbor embedding (t-SNE)-based algorithm 20 21…”

Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease

“…In a mouse model of colitis, intraperitoneal injection of BMMSCs could regulate the immunomodulatory effects of B cells by upregulating IL-10 expression, induce a regulatory B-cell (Breg) population characterized by CD23 and CD43 phenotypic markers, increase the number of CD23 + , CD43 + , and Breg cells, reduce the clinical and pathological severity of colitis in mice ( Chen et al, 2019a ). Researchers studied the interactions of BM-MSCs and placental MSCs (P-MSCs) in the mouse model, found that P-MSCs could inhibit the proliferation and further differentiation of B cells ( Lee et al, 2021 ).…”