Oct4-negative multipotent adult progenitor cells and mesenchymal stem cells as regulators of T-cell alloreactivity in mice

2011 ◽  
Vol 137 (1-2) ◽  
pp. 78-81 ◽  
Author(s):  
Ariane Luyckx ◽  
Lien De Somer ◽  
Sandra Jacobs ◽  
Omer Rutgeerts ◽  
Caroline Lenaerts ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Progenitor Cells ◽  
Multipotent Adult Progenitor Cells

scholarly journals Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells

2013 ◽  
Vol 91 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Sandra A Jacobs ◽  
Valerie D Roobrouck ◽  
Catherine M Verfaillie ◽  
Stefaan W Van Gool
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Human Mesenchymal Stem Cells ◽  
Multipotent Adult Progenitor Cells

scholarly journals Multipotent adult progenitor cells can suppress graft-versus-host disease via prostaglandin E2 synthesis and only if localized to sites of allopriming

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 693-701 ◽  
Author(s):  
Steven L. Highfill ◽  
Ryan M. Kelly ◽  
Matthew J. O'Shaughnessy ◽  
Qing Zhou ◽  
Lily Xia ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Prostaglandin E2 ◽  
Progenitor Cells ◽  
T Cell Activation ◽  
Graft Versus Host Disease ◽  
Cell Activation ◽  
Multipotent Adult Progenitor Cells ◽  
Graft Versus Host

Abstract Multipotent adult progenitor cells (MAPCs) are nonhematopoietic stem cells capable of giving rise to a broad range of tissue cells. As such, MAPCs hold promise for tissue injury repair after transplant. In vitro, MAPCs potently suppressed allogeneic T-cell activation and proliferation in a dose-dependent, cell contact–independent, and T-regulatory cell–independent manner. Suppression occurred primarily through prostaglandin E2 synthesis in MAPCs, which resulted in decreased proinflammatory cytokine production. When given systemically, MAPCs did not home to sites of allopriming and did not suppress graft-versus-host disease (GVHD). To ensure that MAPCs would colocalize with donor T cells, MAPCs were injected directly into the spleen at bone marrow transplantation. MAPCs limited donor T-cell proliferation and GVHD-induced injury via prostaglandin E2 synthesis in vivo. Moreover, MAPCs altered the balance away from positive and toward inhibitory costimulatory pathway expression in splenic T cells and antigen-presenting cells. These findings are the first to describe the immunosuppressive capacity and mechanism of MAPC-induced suppression of T-cell alloresponses and illustrate the requirement for MAPC colocalization to sites of initial donor T-cell activation for GVHD inhibition. Such data have implications for the use of allogeneic MAPCs and possibly other immunomodulatory nonhematopoietic stem cells for preventing GVHD in the clinic.

scholarly journals Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Qiuli Liu ◽  
Xiaoyong Chen ◽  
Chang Liu ◽  
Lijie Pan ◽  
Xinmei Kang ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Liver Injury ◽  
T Cell Activation ◽  
Gene Set Enrichment Analysis ◽  
Human Umbilical Cord ◽  
Con A ◽  
Immune Mediated

AbstractLiver diseases with different pathogenesis share common pathways of immune-mediated injury. Chitinase-3-like protein 1 (CHI3L1) was induced in both acute and chronic liver injuries, and recent studies reported that it possesses an immunosuppressive ability. CHI3L1 was also expressed in mesenchymal stem cells (MSCs), thus we investigates the role of CHI3L1 in MSC-based therapy for immune-mediated liver injury here. We found that CHI3L1 was highly expressed in human umbilical cord MSCs (hUC-MSCs). Downregulating CHI3L1 mitigated the ability of hUC-MSCs to inhibit T cell activation, proliferation and inflammatory cytokine secretion in vitro. Using Concanavalin A (Con A)-induced liver injury mouse model, we found that silencing CHI3L1 significantly abrogated the hUC-MSCs-mediated alleviation of liver injury, accompanying by weakened suppressive effects on infiltration and activation of hepatic T cells, and secretion of pro-inflammatory cytokines. In addition, recombinant CHI3L1 (rCHI3L1) administration inhibited the proliferation and function of activated T cells, and alleviated the Con A-induced liver injury in mice. Mechanistically, gene set enrichment analysis showed that JAK/STAT signalling pathway was one of the most significantly enriched gene pathways in T cells co-cultured with hUC-MSCs with CHI3L1 knockdown, and further study revealed that CHI3L1 secreted by hUC-MSCs inhibited the STAT1/3 signalling in T cells by upregulating peroxisome proliferator-activated receptor δ (PPARδ). Collectively, our data showed that CHI3L1 was a novel MSC-secreted immunosuppressive factor and provided new insights into therapeutic treatment of immune-mediated liver injury.

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