Treatment of Inflammatory Diseases with Mesenchymal Stem Cells (original) (raw)
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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.
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.
Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy
World journal of stem cells, 2014
Mesenchymal stem cells (MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produc...
Chronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation.
Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies
Expert Opinion on Biological Therapy, 2008
Background : Mesenchymal stem cells (MSC) are multipotent cells that can be isolated from the bone marrow and expanded in culture relatively easily. Culture-expanded MSC have been used in clinical settings to enhance hematopoietic stem cell engraftment in bone marrow transplant patients and in tissue regeneration therapy. More recently, the anti-inflammatory effects of MSC have generated a great deal of interest. Objective/methods : In this review we describe in vitro assays that have demonstrated how MSC regulate immune cell proliferation, differentiation and phenotype. We also highlight effector molecules produced by MSC that drive this function. In addition, we focus on animal models of lung injury, in which administration of MSC attenuates inflammation, and injury revealing a central role for MSC in mitigating pro-inflammatory networks and amplifying anti-inflammatory signals. Conclusions : The discoveries described herein have contributed to the novel concept of MSC as a therapeutic modality in inflammatory diseases, including acute lung injury.
Stem Cells International, 2022
Autoimmune diseases, chronic in nature, are generally hard to alleviate. Present long-term treatments with available drugs such as steroids, immune-suppressive drugs, or antibodies have several debilitating side effects. Therefore, new treatment options are urgently needed. Stem cells, in general, have the potential to reduce immune-mediated damage through immunomodulation and T cell regulation (T regs) by inhibiting the proliferation of dendritic cells and T and B cells and reducing inflammation through the generation of immunosuppressive biomolecules like interleukin 10 (IL-10), transforming growth factor-β (TGF-β), nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), and prostaglandin E2 (PGE2). Many stem cell-based therapeutics have been evaluated in the clinic, but the overall clinical outcomes in terms of efficacy and the longevity of therapeutic benefits seem to be variable and inconsistent with the postulated benefits. This emphasizes a greater need for building robust preclinical models and models that can better predict the clinical translation of stem cell-based therapeutics. Stem cell therapy based on MSCs having the definitive potential to regulate the immune system and control inflammation is emerging as a promising tool for the treatment of autoimmune disorders while promoting tissue regeneration. MSCs, derived from bone marrow, umbilical cord, and adipose tissue, have been shown to be highly immunomodulatory and anti-inflammatory and shown to enhance tissue repair and regeneration in preclinical models as well as in clinical settings. In this article, a review on the status of MSCbased preclinical disease models with emphasis on understanding disease mechanisms in chronic inflammatory disorders caused by exaggerated host immune response in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was carried out. We also emphasized various factors that better predict the translation of stem cell therapeutic outcomes from preclinical disease models to human patients.
Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment
Journal of Inflammation Research, 2016
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 tissuespecific 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.
Mesenchymal Stem Cell treatment for autoimmune diseases: a critical review
Biological Research, 2012
Mesenchymal stem cells (MSCs) are now known to display not only stem cell multipotency, but also robust antiinfl ammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn´s disease, multiple sclerosis, refractory systemic lupus erythematosus and systemic sclerosis. Current data suggests that MSCs may not only replace diseased tissues, but also exert several trophic, regenerative and antiinfl ammatory eff ects. While the clinical outcome in case reports and phase I-II trials seems occasionally striking, these limited results point to the need to perform controlled multicenter trials. Future advances from stem cell science can be expected to pinpoint signifi cant MSC subpopulations and/or stem cell markers for improved regenerative or immunoregulatory properties.
Human Mesenchymal Stem/Stromal Cells in Immune Regulation and Therapy
Stem Cells Translational Medicine, 2022
Studies of mesenchymal stem (or stromal) cells (MSCs) have moved from bedside to bench and back again. The stromal cells or fibroblasts are found in all tissues and participate in building the extracellular matrix (ECM). Bone marrow (BM)-derived MSCs have been studied for more than 50 years and have multiple roles. They function as stem cells and give rise to bone, cartilage, and fat in the BM (these are stem cells); support hematopoiesis (pericytes); and participate in sensing environmental changes and balancing pro- and anti-inflammatory conditions. In disease states, they migrate to sites of injury and release cytokines, hormones, nucleic acids depending on the microenvironment they find. Clinicians have begun to exploit these properties of BM, adipose tissue, and umbilical cord MSCs because they are easy to harvest and expand in culture. In this review, I describe the uses to which MSCs have been put, list ongoing clinical trials by organ system, and outline how MSCs are thought...