Mesenchymal stromal cell ‘licensing’: a multistep process

Krampera, Mauro

doi:10.1038/leu.2011.108

Cited by 314 publications

(332 citation statements)

References 106 publications

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“…Alterations in this sequence of events result in inadequate organ repair giving rise to pathologic states [11,19,68,69]. Inflammatory priming has been viewed as a requirement for MSCs to have immune modulatory properties in vitro and in vivo [4][5][6][11][12][13][14]. The origin of MSCs, the secretion of soluble factors conferring proper SC licensing, and the level of inflammation at the site of cell delivery may account for some of the differences FIG.…”

Section: Discussionmentioning

confidence: 99%

“…reported in the literature [12]. However, the immune modulatory function of BM-MSCs has been documented in graftversus-host disease [4][5][6], autoimmune encephalomyelitis [17], sepsis [3], collagen-induced arthritis, and bowel inflammation [15,16,20].…”

mentioning

confidence: 99%

“…However, it is still unclear whether allogenic adult SCs are rejected by the host immune system due to histoincompatibility [9] or resident SCs per se interfere with the physiological function of the host immune system. Several SC subtypes, including neural SCs [10] and mesenchymal stromal cells (MSCs) [11][12][13][14], possess regenerative potential and may interact with immune effector cells (IECs), profoundly influencing their function in vitro and in vivo. The immune system plays a critical role in the pathogenesis and progression of a number of degenerative diseases, raising the possibility that SCs may be effective in repairing the damaged organ by promoting cell formation and modulating the associated immune response [6,[14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Comparative study of immune regulatory properties of stem cells derived from different tissues

et al. 2014

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative study of immune regulatory properties of stem cells derived from different tissues

et al. 2014

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“…However, this broad regulatory capacity is not a constitutive property of MSCs, instead requiring an activation step to induce it, a phenomenon known as "priming". [11] In this regard, the focus of this study was to investigate the functional role of NF-κB in the "priming" of MSCs in an inflammatory environment; in particular, the importance of the TNF-α/NF-κB axis.…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

Dorronsoro¹,

Ferrin²,

Salcedo³

et al. 2013

Eur J Immunol

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Although mesenchymal stromal cells (MSCs) possess the capacity to modulate immune responses, little is known about the mechanisms that underpin these processes. In this study, we show that immunosupression is mediated by activation of nuclear factor kappa B (NF-κB) in human MSCs. This pathway is activated by TNF-α that is generated following TCR stimulation of T cells. Inhibition of NF-κB through silencing of IκB kinase β or the TNF-α receptor abolishes the immunosuppressive capacity of MSCs. Our data also indicate that MSC-associated NF-κB activation primarily leads to inhibition of T-cell proliferation with little effect on expression of the activation markers CD69 and CD25. Thus, our data support the hypothesis that the TNF-α/NF-κB signalling pathway is required for the initial priming of immunosuppressive function in human MSCs. Interestingly, drugs that interfere with NF-κB activation significantly antagonise the immunoregulatory effect of MSCs, which could have important implications for immunosuppression regimens in the clinic. Keywords:Immunoregulation r MSC r NF-κB r TNF-α See accompanying Commentary by Pistoia and RaffaghelloAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMesenchymal stromal cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into multiple lineages. These cells are found in a variety of tissues during development, of which BM represents the most common source for research purposes. From a clinical perspective, MSCs are considered to Correspondence: Dr. César Trigueros e-mail: ctrigueros@inbiomed.org have a potential use in tissue repair for bone, cartilage and tendon. However, due to their immunomodulatory properties and their inclusion as a stromal component of the marrow microenvironment, MSCs are currently utilised in other therapeutic scenarios, such as those encountered in hematopoietic stem cell transplantation, GVH disease or chronic inflammatory diseases [1,2]. These characteristics, together with their low immunogenicity [1,2], have opened up promising new avenues of research for the use of MSCs not only in autologous but also in allogeneic settings.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 480-488 Immunomodulation 481 The immunomodulatory activity of MSCs, directed against a wide range of effector cells of both the innate and adaptive immune system, has been described. Communication between MSCs and immune cells, through cell-to-cell contact-dependent and/or contact-independent mechanisms, has been shown to lead to increased production of soluble immunomodulatory factors such as indoleamine 2,3-deoxigenase [3,4], prostaglandin E2 [5][6][7], iNOS [8], transforming growth factor β (TGF-β), hepatocyte growth factor [9], human lymphocytes Ag molecule 5 and IL-10 [10]. Thus, the picture is complex, as it is likely that multiple regulatory mechanisms exist without an obvious hierarchy of importance.The inflammatory e...

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“…A group of cytokines that produced within inflammatory milieu are responsible for the licensing of MSCs and can act alone e.g. IFN-g or in combination [42]. IFN-g can trigger the proliferation and immunomodulatory function of MSCs via the Kynurenine-dependent mechanism [43].…”

Section: Preparation For the Repair Phase; Licensing Of Mscsmentioning

confidence: 99%

The roles of immune cells in bone healing; what we know, do not know and future perspectives

El-Jawhari

Jones

Giannoudis

2016

Injury

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Mesenchymal stromal cell ‘licensing’: a multistep process

Cited by 314 publications

References 106 publications

Comparative study of immune regulatory properties of stem cells derived from different tissues

Comparative study of immune regulatory properties of stem cells derived from different tissues

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

The roles of immune cells in bone healing; what we know, do not know and future perspectives

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