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

Division of Hematology/Oncology, Department of Medicine, Case Comprehensive Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Experimental Hematology (Impact Factor: 2.81). 09/2005; 33(8):928-34. DOI: 10.1016/j.exphem.2005.05.002
Source: PubMed

ABSTRACT Human bone marrow-derived mesenchymal cells (MSCs) are precursors of nonhematopoietic mesenchymal cells of the bone marrow microenvironment. MSCs were shown to inhibit alloreactive T lymphocytes, but the mechanism and mediators of this effect are not fully understood. Here we describe a novel interaction between blood monocytes and bone marrow-derived, culture-expanded MSCs, which results in inhibition of T-lymphocyte activation. We found that CD14+ monocytes from blood activate MSCs to secrete inhibitory molecules that lead to inhibition of alloreactive T cells. This cellular communication is not contact-dependent, but rather is mediated by soluble factors that include interleukin (IL)-1beta. MSC-mediated inhibition of alloreactive T lymphocytes is associated with downregulation of activation markers CD25, CD38, and CD69 detected both in CD4+ and CD8+ T lymphocytes. The cytokines secreted by MSCs that mediate T-cell inhibition include transforming growth factor-beta1, but not IL-10. The interaction between blood monocytes and the MSCs represents a unique immune regulatory paradigm that can potentially be exploited in clinic.

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    • "In fact, it is well known that MSCs do not stimulate T-cell activation. Some studies have shown that MSCs cause a reduction in the expression of activation markers [26] [27], while others found no change in expression of these markers [22] [28]. Taken together, the ability of MSCs to escape from immune response and to modulate T-cell proliferation renders them attractive candidates for use in cell therapy. "
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    ABSTRACT: Mesenchymal stromal cells (MSCs) are multipotent cells, which can give rise to several cell types including osteoblasts, adipocytes, and chondroblasts. These cells can be found in a variety of adult and fetal tissues, such as bone marrow, adipose tissue, cord blood, and placenta. In recent years, the biological properties of MSCs have attracted the attention of researchers worldwide due to their potential application for treating a series of clinical situations. Among these properties, special attention should be given to the immunoregulatory potential of those cells. MSCs are able to act on all cells of the immune system, which includes the capacity to inhibit the proliferation and function of T-cells. This feature renders them natural candidates to treat several diseases in which cellular immune response is exacerbated. In this review, we outline the main mechanisms by which MSCs immunosuppress T-cell response, focusing on cell-cell contact, secretion of soluble factors, and regulatory T-cell generation. The influence of surface markers in the immunosuppression process and features of MSCs isolated from different sources are also discussed. Finally, the influences of toll-like receptors and cytokines on the inflammatory microenvironment are highlighted regarding the activation of MSCs to exert their immunoregulatory function.
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    • "Finally, MSCs might also be anti-inflammatory through inhibition of IFN-γ and TNF-α and stimulation of metalloproteinase inhibitors and anti-inflammatory interleukins such as IL-10 (Caplan 2009). The most exciting element of the MSC is their apparent exquisite responsiveness to their micro-environment, in that they behave according to the environment in which they are placed (Groh et al. 2005; Prockop 2009). In this manner, MSCs would respond appropriately to the degree of disease and modulate the local environment in favour of reduced inflammation, reduced apoptosis and/or enhanced matrix synthesis by endogenous progenitors and tissue specific cells. "
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    • "To which extent HGF, constrictively expressed in MSC [16], plays a role in MSC-mediated immunosuppression still remains unclear. While some authors point out a role for this factor alone or demonstrating additive effect together with TGF-í µí»½ [12] [20], others discard its function in immunoregulation , rather attributing its existence in cocultures to its production by lymphocytes [21]. Finally, HLA-G5, a nonclassical HLA class I molecule, has first been shown in the maternal tolerance to the fetus by mediating inhibition of NK cell cytotoxicity. "
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