Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells

Groh, Margaret E.; Maitra, Basabi; Szekely, Emese; Koç, Omer N.

doi:10.1016/j.exphem.2005.05.002

Cited by 340 publications

(282 citation statements)

References 17 publications

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“…Allogenic MSCs from any passage did not elicit the upregulation of CD69 and CD25 on T cells, indicating that long-term culture did not impair the low immunogenicity of MSCs (data not shown); while MSCs significantly inhibited PHA-induced upregulation of CD69 and CD25, which is consistent with previous reports (21)(22)(23) no MSCs control), respectively, when MSCs from P7 were added to the co-culture. The addition of MSCs from P13 did not exert any suppressive influences on the expression of activation antigens on the PHA-stimulated T cells (for both CD25 and CD69, P>0.05 vs. no MSCs control; Fig.…”

Section: Effects Of Mscs In Long-term Culture On the Activation Of T supporting

confidence: 81%

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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Abstract. Improved knowledge of the immunological properties of mesenchymal stem cells (MSCs) creates a potential cell-mediated immunotherapeutic approach for arthritic diseases. The low frequency of MSCs necessitates their in vitro expansion prior to clinical use. As sequential passage has been used as the most popular strategy for expansion of MSCs, the effect of long-term culture on the immunological properties of MSCs is not clear. In this study, we observed that the morphology of MSCs showed the typical characteristics of the Hayflick model of cellular aging during sequential expansion. The growth kinetics of MSCs decreased while the number of MSCs staining positive for SA β-gal (senescence marker) increased in long-term culture. Although long-term culture exerts less of an effect on the immunophenotype of MSCs, the immunosuppressive effects of MSCs on the allogeneic T-cell proliferation, activation-antigen expression (CD69 and CD25) and cytokine production (IFN-γ, TNF-α, IL-10) were significantly impaired following stimulation with phytohemagglutinin (PHA).

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Section: Effects Of Mscs In Long-term Culture On the Activation Of T supporting

confidence: 81%

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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“…The veto-like (forbidding) activity of MSCs (Potian et al, 2003;Tscherning and Claesson, 1993) inhibits T-cell proliferation (Bartholomew et al, 2002;Bocelli-Tyndall et al, 2007;Di Nicola et al, 2002;Klyushnenkova et al, 2005) via induction of T-cell quiescence upon blockade into G0/G1 (Glennie et al, 2005) and downregulation of the T-cell activation markers CD25, CD38, and CD69 (Groh et al, 2005;Le Blanc et al, 2004) and of IL-2 production (Park et al, 2011). MSCs also inhibit Th17 differentiation from both naïve and memory T cell precursors in vitro, as well as preventing the efflux of naturally occurring Th17 cells derived from inflammation sites in vivo (Duffy et al, 2011).…”

Section: Modulation Of Immune Responsesmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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“…These features are likely to represent the basis for MSC homing to multiple organs where they undergo a program of tissue-specific differentiation [36]. Despite the current lack of information on Toll-like receptor (TLR) expression, MSC are profoundly influenced by microenvironmental factors and can respond to some inflammatory cytokines such as IL-1b [37], IL-17 [38] and (more importantly) IFN-c, all capable of significantly affecting their function. In this context, it is worth stressing that while under some circumstances IFN-c appears to enhance the immunosuppressive activity of human MSC [39], in other cases it can induce MSC to act even as non-conventional antigen-presenting cells (APC) [17,40].…”

Section: Immunological Phenotype and Functions Of Mscmentioning

confidence: 99%

“…Inhibition of cell division could be a possible explanation since accumulation of cells in the G 0 phase of the cell cycle has been detected [45]. In addition, suppression of T cell proliferation induced by human MSC appears to depend, at least in part, on the cross-talk between the two cell populations, leading to the production of inflammatory cytokines such as IFN-c [39] and IL-1b [37] by activated immune cells. Inhibition of T cell proliferation resulted in the decreased production of effector Th1 cytokines [16,42,46]; however, the expression of activation markers in T cells that have been cultured with MSC remains a controversial issue [39,43,45,47].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells

Cited by 340 publications

References 17 publications

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

How stem cells speak with host immune cells in inflammatory brain diseases

Immunoregulatory function of mesenchymal stem cells

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