Multipotent Human Mesenchymal Stromal Cells Mediate Expansion of Myeloid-Derived Suppressor Cells via Hepatocyte Growth Factor/c-Met and STAT3

Mesenchymal stem/stromal cells (MSCs) are progenitors which share plastic-adherence capacity and cell surface markers but have different properties according to their cell and tissue sources and to culture conditions applied. Many recent publications suggest that MSCs can differentiate into hepatic-like cells, which can be a consequence of either a positive selection of rare in vivo pluripotent cells or of the original plasticity of some cells contributing to MSC cultures. A possible role of MSCs in hereditary transmission of obesity and/or diabetes as well as properties of MSCs regarding immunomodulation, cell fusion and exosome release capacities are discussed according to recent literature. Limitations in methods used to track MSCs in vivo especially in the context of liver cirrhosis are addressed as well as strategies explored to enhance their migratory, survival and proliferation properties, which are known to be relevant for their future clinical use. Current knowledge regarding mechanisms involved in liver cirrhosis amelioration mediated by naïve and genetically modified MSCs as well as the effects of applying preconditioning and combined strategies to improve their therapeutic effects are evaluated. Finally, first reports of GMP guidelines and biosafety issues in MSCs applications are discussed.

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“…2). For instance, antifibrotic [99,108,109] and immunomodulatory properties [110,111] were found for HGF as well as for IGF-1 (Fig. 2).…”

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 87%

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Fiore

Mazzolini

Aquino

2015

Stem Cell Rev and Rep

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“…These factors include prostaglandin E2 (PGE2) [73,[79][80][81], indoleamine 2,3-dioxygenase (IDO) [82,83], hepatocyte growth factor (HGF) [84,85] and transforming growth factor (TGF)-β 1 [69,86]. Additionally, it is well-established that IFN-γ plays an important role in the enhancement of MSCs suppressive activity [82].…”

Section: Mscs Inhibit T Cells Proliferation and Suppress Allogeneic Tmentioning

confidence: 99%

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Zhao¹,

Ren

Han

2016

Journal of Cellular Immunotherapy

251

200

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Mesenchymal stem cells (MSCs) represent a heterogenous population of adult,fibroblast-like multi-potent cells. MSCs have drawn much attention during the last decade in the field of regenerative medicine, mainly due to their capacity to differentiate into specific cell types, abundant production of soluble growth factors and cytokines, and hematopoiesis supporting properties. In addition, MSCs can migrate to the sites of inflammation and hold potent of immunomodulatory and anti-inflammatory effects through cell and cell interactions between MSCs and lymphocytes or production of soluble factors. Therefore, the application of MSCs in many disease situations is full of possibilities for future clinical treatment. Phase III clinical trials have been run using

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“…Specifically, the gp130-STAT3 signaling axis promotes recruitment of immature myeloid cells (“Myeloid-Derived Suppressor Cells”, MDSCs) that regulate innate immune inflammation (41). In a further link between the acute-phase response and innate immunity, MDSCs can be induced by HGF (42). …”

Section: Afferent and Efferent Innate Immune Signalsmentioning

confidence: 99%

Hepatocytes as Immunological Agents

Crispe

2016

The Journal of Immunology

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Hepatocytes are targeted for infection by a number of major human pathogens, including Hepatitis B Virus, Hepatitis C Virus and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses including ischemia, physical trauma and sepsis. They express a variety of innate immune receptors and when challenged with Pathogen- or Damage-Associated Molecular Patterns, can deliver cell-autonomous innate immune responses that may result in host defense, or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias towards immune tolerance.

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Multipotent Human Mesenchymal Stromal Cells Mediate Expansion of Myeloid-Derived Suppressor Cells via Hepatocyte Growth Factor/c-Met and STAT3

Cited by 127 publications

References 52 publications

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Hepatocytes as Immunological Agents

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