B Lymphocytes as Targets of the Immunomodulatory Properties of Human Amniotic Mesenchymal Stromal Cells

Magatti, Marta; Masserdotti, Alice; Signoroni, Patrizia Bonassi; Vertua, Elsa; Stefani, Francesca Romana; Silini, Antonietta; Parolini, Ornella

doi:10.3389/fimmu.2020.01156

Cited by 36 publications

(34 citation statements)

References 80 publications

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“…In keeping with the known immunomodulation of P‐MSCs toward T cells, NKs, and myeloid cells, our findings here further extend those immunomodulatory properties toward peripheral B cells, with significant induction of multiple populations of IL‐10‐producing Bregs compared to BM‐MSCs. Indeed, an increasing number of studies show that fetal‐source umbilical cord‐MSCs suppress in vitro B‐cell proliferation and halt terminal differentiation 55,56 ; two very recent reports using amniotic membrane‐MSCs demonstrate similar findings, 57 and decreased pulmonary B‐cell recruitment and maturation was found in an in vivo lung injury model 58 . Moreover, our lab and others have found that fetal‐source MSCs 29,59 —in contrast to adult BM‐MSCs 60 —may not require inflammatory priming for immunomodulation, an aspect that has not been evaluated for MSC interactions with B cells.…”

Section: Discussionmentioning

confidence: 96%

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

Lee

Wang

Yen

et al. 2021

Stem Cells Translational Medicine

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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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Section: Discussionmentioning

confidence: 96%

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

Lee

Wang

Yen

et al. 2021

Stem Cells Translational Medicine

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“…Further analyses have shown that MSCs also markedly inhibit the pDC-induced maturation of B cells. Similarly, Magatti et al (2020) reported a decreased proliferation, maturation, and antibody secretion mediated by MSCs. They also demonstrated that the conditioned medium of MSCs reduces the expression of CD205, CD14, and Toll-like receptor 9 by B cells and that the observed effects are partially mediated by PGE2.…”

Section: Regulation Of Adaptive Immunity By Mscsmentioning

confidence: 94%

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

Müller

Tunger

Wobus

et al. 2021

Front. Cell Dev. Biol.

110

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Mesenchymal stromal cells (MSCs) are characterized by an extraordinary capacity to modulate the phenotype and functional properties of various immune cells that play an essential role in the pathogenesis of inflammatory disorders. Thus, MSCs efficiently impair the phagocytic and antigen-presenting capacity of monocytes/macrophages and promote the expression of immunosuppressive molecules such as interleukin (IL)-10 and programmed cell death 1 ligand 1 by these cells. They also effectively inhibit the maturation of dendritic cells and their ability to produce proinflammatory cytokines and to stimulate potent T-cell responses. Furthermore, MSCs inhibit the generation and proinflammatory properties of CD4+ T helper (Th)1 and Th17 cells, while they promote the proliferation of regulatory T cells and their inhibitory capabilities. MSCs also impair the expansion, cytokine secretion, and cytotoxic activity of proinflammatory CD8+ T cells. Moreover, MSCs inhibit the differentiation, proliferation, and antibody secretion of B cells, and foster the generation of IL-10-producing regulatory B cells. Various cell membrane-associated and soluble molecules essentially contribute to these MSC-mediated effects on important cellular components of innate and adaptive immunity. Due to their immunosuppressive properties, MSCs have emerged as promising tools for the treatment of inflammatory disorders such as acute graft-versus-host disease, graft rejection in patients undergoing organ/cell transplantation, and autoimmune diseases.

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“…Given these premises, strategies affecting B cells and their activation status may represent a valid therapeutic approach in PE. Perinatal derivatives constitute a promising tool in this context, especially in the light of the recent identification of B cells as a target of their immune modulatory action [ 85 , 86 ]. The next paragraphs outline the state of the art of the crosstalk between perinatal derivatives and B cells and the potential for this interaction to be translated into a valid therapeutic option for PE.…”

Section: Focus On B Cellsmentioning

confidence: 99%

The Role of B Cells in PE Pathophysiology: A Potential Target for Perinatal Cell-Based Therapy?

Magatti

Masserdotti

Cargnoni

et al. 2021

IJMS

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The pathophysiology of preeclampsia (PE) is poorly understood; however, there is a large body of evidence that suggests a role of immune cells in the development of PE. Amongst these, B cells are a dominant element in the pathogenesis of PE, and they have been shown to play an important role in various immune-mediated diseases, both as pro-inflammatory and regulatory cells. Perinatal cells are defined as cells from birth-associated tissues isolated from term placentas and fetal annexes and more specifically from the amniotic membrane, chorionic membrane, chorionic villi, umbilical cord (including Wharton’s jelly), the basal plate, and the amniotic fluid. They have drawn particular attention in recent years due to their ability to modulate several aspects of immunity, making them promising candidates for the prevention and treatment of various immune-mediated diseases. In this review we describe main findings regarding the multifaceted in vitro and in vivo immunomodulatory properties of perinatal cells, with a focus on B lymphocytes. Indeed, we discuss evidence on the ability of perinatal cells to inhibit B cell proliferation, impair B cell differentiation, and promote regulatory B cell formation. Therefore, the findings discussed herein unveil the possibility to modulate B cell activation and function by exploiting perinatal immunomodulatory properties, thus possibly representing a novel therapeutic strategy in PE.

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B Lymphocytes as Targets of the Immunomodulatory Properties of Human Amniotic Mesenchymal Stromal Cells

Cited by 36 publications

References 80 publications

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

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

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

The Role of B Cells in PE Pathophysiology: A Potential Target for Perinatal Cell-Based Therapy?

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