Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment

Abstract

Human mesenchymal stem cells (MSCs) are considered to be a promising source of cells in regenerative medicine. They have large potential to differentiate into various tissue-specific populations and may be isolated from diverse tissues in desired quantities. As cells of potential autologous origin, they allow recipients to avoid the alloantigen responses. They also have the ability to create immunomodulatory microenvironment, and thus help to minimize organ damage caused by the inflammation and cells activated by the immune system. Our knowledge about the reparative, regenerative, and immunomodulatory properties of MSCs is advancing. At present, there is a very comprehensible idea on how MSCs affect the immune system, particularly in relation to the tissue and organ damage on immunological basis. Hitherto a number of effective mechanisms have been described by which MSCs influence the immune responses. These mechanisms include a secretion of soluble bioactive agents, an induction of regulatory T cells, modulation of tolerogenic dendritic cells, as well as induction of anergy and apoptosis. MSCs are thus able to influence both innate and adaptive immune responses. Soluble factors that are released into local microenvironment with their subsequent paracrine effects are keys to the activation. As a result, activated MSCs contribute to the restoration of damaged tissues or organs through various mechanisms facilitating reparative and regenerative processes as well as through immunomodulation itself and differentiation into the cells of the target tissue.

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…Mesenchymal stem cells act similarly toward B and NK cells [55]. Overall, these data revealed a marked crosstalk between osteosarcoma cells, mesenchymal stem cells and immune cells in favor to the tumor development and metastatic process.…”

“…Activated mesenchymal stem cells can exhibit immunomodulatory properties [55][56][57]. In this context, IFN- synergizes with TNF- and/or IL-1 for activating mesenchymal stem cells which become immunosuppressive and then can inhibit T cell proliferation [56].…”

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…First, they have a remarkable ability to proliferate in vitro and differentiate into many (but not all) cell types. Second, they are endowed with migration and homing properties through which they can reach damaged tissues [21]. Finally, they exhibit immunomodulatory properties; they avoid allorecognition through the low expression of major histocompatibility complex (MHC) class I and the absence of MHC class II, and they generate a local immunosuppressive microenvironment through the secretion of cytokines [22].…”

An engineered biomarker system to monitor and modulate immune clearance of cell therapies

“…A potential reason why non-autologous cells persist longer may also be due to the slight inflammatory environment created by their immunogenicity. The activation and creation of a pro-inflammatory MSC state is known to enhance MSC function which has the potential to increase their ability for immune evasion 46 .…”