A critical role of IFNgamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1.
Huiming Sheng,Ying Wang,Yuqing Jin,Qiuyu Zhang,Yan Zhang,Li Wang,Baihua Shen,Shuo Yin,Wei Liu,Lei Cui,Ningli Li +10 more
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It is suggested that IFNγ plays a critical role in triggering the immunosuppresion by MSCs through up-regulating B7-H1 in these cells, and evidence supporting the cell-cell contact mechanism in MSC-mediated immunosppression is provided.Abstract:
Bone-marrow-derived mesenchymal stem cells (MSCs) have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability of MSCs. The precise mechanisms underlying MSC-mediated immunosuppression remain largely undefined, although both cell-cell contact and soluble factors have been implicated; nor is it clear how the immunosuppressive property of MSCs is modulated by T cells. Using MSCs isolated from mouse bone marrow, we show here that interferon gamma (IFNgamma), a well-known proinflammatory cytokine produced by activated T cells, plays an important role in priming the immunosuppressive property of MSCs. Mechanistically, IFNgamma acts directly on MSCs and leads to up-regulation of B7-H1, an inhibitory surface molecule in these stem cells. MSCs primed by activated T cells derived from IFNgamma-/- mouse exhibited dramatically reduced ability to suppress T cell proliferation, a defect that can be rescued by supplying exogenous IFNgamma. Moreover, siRNA-mediated knockdown of B7-H1 in MSCs abolished immunosuppression by these cells. Taken together, our results suggest that IFNgamma plays a critical role in triggering the immunosuppresion by MSCs through up-regulating B7-H1 in these cells, and provide evidence supporting the cell-cell contact mechanism in MSC-mediated immunosuppression.read more
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Human mesenchymal stem cells - current trends and future prospective
TL;DR: Recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials are highlighted.
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Mesenchymal stem cells and immunomodulation: current status and future prospects
Fei Gao,Sm M. Chiu,Dal A. L. Motan,Zhao Zhang,L. Chen,Hong-Lin Ji,Hf-F. Tse,Qinf-Ling Fu,Qizhou Lian +8 more
TL;DR: The preclinical and clinical studies of MSCs from different adult tissues are summarized, the current hurdles to their use are discussed, and the future development of pluripotent stem cell-derived M SCs are proposed as an approach to immunomodulation therapy.
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Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis
TL;DR: Takeaway is that gingiva-derived mesenchymal stem cells can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases.
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Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives.
TL;DR: This review will highlight the discovery of theParacrine mechanism of MSCs, regulation of the paracrine biology of MCCs, important paracine factors of M SCs in modulation of tissue repair, exosome and mitochondrial transfer for tissue repair and the future perspective for MSC-based therapy.
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TL;DR: Current understanding of the immunomodulatory mechanisms of MSCs and issues related to their therapeutic application are discussed, which suggest the plasticity of immunoregulation by M SCs is controlled by the intensity and complexity of inflammatory stimuli.
References
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Multilineage Potential of Adult Human Mesenchymal Stem Cells
Mark F. Pittenger,Alastair Morgan Mackay,Stephen C. Beck,Rama K. Jaiswal,Robin Douglas,Joseph D. Mosca,Mark Aaron Moorman,Donald William Jr. Ward Road Simonetti,Stewart Craig,Daniel R. Marshak +9 more
TL;DR: Adult stem cells isolated from marrow aspirates of volunteer donors could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages.
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Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
Gordon J. Freeman,Andrew J. Long,Yoshiko Iwai,Karen Bourque,Tatyana Chernova,Hiroyuki Nishimura,Lori Fitz,Nelly Malenkovich,Taku Okazaki,Michael C. Byrne,Heidi F. Horton,Lynette A. Fouser,Laura L. Carter,Vincent Ling,Michael R Bowman,Beatriz M. Carreno,Mary Collins,Clive Wood,Tasuku Honjo +18 more
TL;DR: It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.
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Human mesenchymal stem cells modulate allogeneic immune cell responses
TL;DR: Insight is offered into the interactions between allogeneic MSCs and immune cells and mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation.
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Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli
Massimo Di Nicola,Carmelo Carlo-Stella,Michele Magni,Marco Milanesi,Paolo Longoni,Paola Matteucci,Salvatore Grisanti,Alessandro M. Gianni +7 more
TL;DR: The data demonstrate that autologous or allogeneic BMSCs strongly suppress T-lymphocyte proliferation, this phenomenon that is triggered by both cellular as well as nonspecific mitogenic stimuli has no immunologic restriction, and T-cell inhibition is not due to induction of apoptosis and is likely due to the production of soluble factors.
Journal ArticleDOI
Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells
Katarina Le Blanc,Ida Rasmusson,Berit Sundberg,Cecilia Götherström,Moustapha Hassan,Mehmet Uzunel,Olle Ringdén +6 more
TL;DR: It is postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo and are transplanted in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver.