The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy (original) (raw)
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Immunomodulatory mechanisms of mesenchymal stem cells and their therapeutic applications
Cellular Immunology, 2017
In the recent years, many studies have shown that MSCs must be stimulated by pro-inflammatory cytokines or other immune mediators before they can modulate immune cells in inflamed and damaged tissues. MSCs appear to be involved in inducing several regulatory immune cells, such as Tregs, Bregs, and regulatory NK cells. This new immune milieu created by MSCs may establish a tolerogenic environment that leads to an optimal condition for the treatment of immune diseases. The mechanisms of MSC action to treat immune disorders need to be further investigated in more detail. Since there have been some contradictory outcomes of clinical trials, it is necessary to perform large-scale and randomized clinical studies, such as a phase 3 placebo-controlled doubleblind study of a third party MSCs to optimize MSC administration and to prove safety and efficacy of MSC treatment. MSCs offer great therapeutic promise, especially for the treatment of difficult-to-treat immune diseases.
Mesenchymal Stem Cells Modulate the Immune System in Developing Therapeutic Interventions
Immune Response Activation [Working Title]
Mesenchymal stem cells (MSCs) are emerging as key players in regenerative medicine for the treatment of various diseases associated with the inflammation and degeneration, thereby aiding in therapeutic advancements. Several tissues have been identified as potential sources of MSCs including the bone marrow, cord blood, dental pulp, umbilical cord, adipose tissue, peripheral blood, and fetal liver, of which some are clinically recognized. MSCs are capable of differentiating into cells of multiple lineages and therefore established as suitable candidates for transplantation in damaged organs. They have added advantage of higher proliferation, easy expansion, and, more importantly, the absence of HLA class II receptors, with potential applications extending toward allogenic settings. MSCs are actively involved in different mechanisms related to repair and regeneration of tissues via immunomodulation, transdifferentiation, paracrine factors, etc. They are known to exhibit profound immunomodulatory effect on T and B cells and natural killer (NK) cells mediated via soluble factors and direct cell-cell contact. The MSCs activate the immune responses and inhibit proliferation, maturation, and differentiation of T and B cells. The MSC-activated immune responses induce the expression of regulatory T cells (Tregs). A plethora of studies have established that MSCs suppress immune responses via immunomodulation that makes them a preferred cell source for the use in clinical trials.
Immunosuppressive Properties of Mesenchymal Stem Cells
Stem Cell Reviews and Reports, 2011
Mesenchymal stem cells (MSC) can be isolated from different adult tissues including bone marrow, adipose tissue, cord blood and placenta. MSCs modulate the immune function of the major immune cell populations involved in alloantigen recognition and elimination, including antigen presenting cells, T cells, B cells and natural killer cells. Many clinical trials are currently underway that employ MSCs to treat human immunological diseases. However, the molecular mechanism that mediates the immunosuppressive effect of MSCs is still unclear and the safety of using MSC in patient needs further confirmation. Here, we review the cytokines that activate MSCs and the soluble factors produced by MSCs, which allow them to exert their immunosuppressive effects. We review the mechanism responsible, at least in part, for the immune suppressive effects of MSCs and highlight areas of research required for a better understanding of MSC immune modulation.
In vitro and In vivo Immunomodulating Properties of Mesenchymal Stem Cells
Recent patents on inflammation & allergy drug discovery, 2018
Mesenchymal stem cells (MSCs) are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into all cell types of mesodermal origin, such as adipocytes, osteocytes and chondrocytes. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Besides the differentiation potential of MSCs, these also regulate the immune response in numerous ailments. The present review expeditesthe immunomodulating prospective of MSCs. Scrupulous search of the literature and patents available on MSCs and their role in the immunomodulation was carried outusing Medline, PubMed, PubMed Central, Science Direct and other scientific databases. The retrieved information has been analyzed and compiled. MSCs have unique regulation of microenvironment in the host tissue by secreting cytokines and immune-receptors which results in immunomodulatory effects. MSCs an effective tool in the treatment of chronic diseases because of its propert...
Mesenchymal stem cells: applications in immuno-cell therapy
Journal of Immunological Sciences, 2018
Mesenchymal stromal cells(MSCs) have been exploited for their immunomodulatory properties in treating various immune-related disorders. MSCs can modulate the immune system through interactions with a variety of immune cells. Regardless of the researchers focused on understanding how MSCs connect to individual immune system cell subsets, the mechanisms for inducing restorative effect still stay mainly undiscovered. Through this mini-review we address what is known about the associations and effects of educated MSCs with cells of the innate immune system (macrophages and neutrophils) and our knowledge of these interactions will be essential in increasing and expanding new medical protocols for MSC based cell therapy in the foreseeable future
Journal of biomedical science, 2016
Human mesenchymal stem cells (MSCs) are multilineage somatic progenitor/stem cells that have been shown to possess immunomodulatory properties in recent years. Initially met with much skepticism, MSC immunomodulation has now been well reproduced across tissue sources and species to be clinically relevant. This has opened up the use of these versatile cells for application as 3rd party/allogeneic use in cell replacement/tissue regeneration, as well as for immune- and inflammation-mediated disease entities. Most surprisingly, use of MSCs for in immune-/inflammation-mediated diseases appears to yield more efficacy than for regenerative medicine, since engraftment of the exogenous cell does not appear necessary. In this review, we focus on this non-traditional clinical use of a tissue-specific stem cell, and highlight important findings and trends in this exciting area of stem cell therapy.
Treatment of Inflammatory Diseases with Mesenchymal Stem Cells
2009
Human mesenchymal stem cells (hMSCs) are rare progenitor cells present in adult bone marrow that have the capacity to differentiate into a variety of tissue types, including bone, cartilage, tendon, fat, and muscle. In addition to multilineage differentiation capacity, MSCs regulate immune and inflammatory responses, providing therapeutic potential for treating diseases characterized by the presence of an inflammatory component. The availability of bone marrow and the ability to isolate and expand hMSCs ex vivo make these cells an attractive candidate for drug development. The low immunogenicity of these cells suggests that hMSCs can be transplanted universally without matching between donors and recipients. MSCs universality, along with the ability to manufacture and store these cells long-term, present a unique opportunity to produce an "off-the-shelf" cellular drug ready for treatment of diseases in acute settings. Accumulated animal and human data support MSC therapeutic potential for inflammatory diseases. Several phase III clinical trials for treatment of acute Graft Versus Host Disease (GVHD) and Crohn's disease are currently in progress. The current understanding of cellular and molecular targets underlying the mechanisms of MSCs action in inflammatory settings as well as clinical experience with hMSCs is summarized in this review.