Anti-inflammatory Properties Of Mesenchymal Stem Cells Research Articles

SOCS3 Protein Mediates the Therapeutic Efficacy of Mesenchymal Stem Cells against Acute Lung Injury

Mesenchymal stem cells (MSCs) have been studied as novel therapeutic agents because of their immunomodulatory properties in inflammatory diseases. The suppressor of cytokine signaling (SOCS) proteins are key regulators of the immune response and macrophage modulation. In the present study, we hypothesized that SOCS in MCSs might mediate macrophage modulation and tested this in a bacteria-induced acute lung injury (ALI) mouse model. The macrophage phenotype was observed in RAW264.7 alveolar macrophages exposed to lipopolysaccharide (LPS) in an in vitro model, and in the ALI mouse model induced by tracheal administration of Escherichia coli (1 × 107 CFU in 0.05mL PBS). In LPS-exposed RAW264.7 cells, the levels of markers of M1 macrophages, such as CD86 and pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α), significantly increased, but they significantly reduced after MSC treatment. Meanwhile, the levels of markers of M2 macrophages, such as CD204 and anti-inflammatory cytokines (IL-4 and IL-10), increased after LPS exposure, and further significantly increased after MSC treatment. This regulatory effect of MSCs on M1/M2 macrophage polarization was significantly abolished by SOCS3 inhibition. In the E. coli-induced ALI model, tissue injury and inflammation in the mouse lung were significantly attenuated by the transplantation of MSCs, but not by SOCS3-inhibited MSCs. The regulatory effect of MSCs on M1/M2 macrophage polarization was observed in the lung injury model but was significantly abolished by SOCS3 inhibition. Taken together, our findings suggest that SOCS3 is an important mediator for macrophage modulation in anti-inflammatory properties of MSCs.

Antiapoptotic Properties of Mesenchymal Stem Cells in a Mouse Model of Corneal Inflammation.

Mesenchymal stem cells (MSCs) represent a population of adult stem cells that have potent immunoregulatory, anti-inflammatory, and antiapoptotic properties. In addition, they have ability to migrate to the site of inflammation or injury, where they contribute to the regeneration and healing process. For these properties, MSCs have been used as therapeutic cells in several models, including treatment of damages or disorders of the ocular surface. If the damage of the ocular surface is extensive and involves a limbal region where limbal stem cell reside, MSC therapy has been proved as the effective treatment approach. Although the anti-inflammatory properties of MSCs have been well characterized, mechanisms of antiapoptotic action of MSCs are not well recognized. Using a chemically damaged cornea in a mouse model, we showed that the injury decreases expression of the gene for antiapoptotic molecule Bcl-2 and increases the expression of proapoptotic genes Bax and p53. These changes were attenuated by local transplantation of MSCs after corneal damage. The antiapoptotic effect of MSCs was tested in an in vitro model of co-cultivation of corneal explants with MSCs. The apoptosis of corneal cells in the explants was induced by proinflammatory cytokines and was significantly inhibited in the presence of MSCs. The antiapoptotic effect of MSCs was mediated by paracrine action, as confirmed by separation of the explants in inserts or by supernatants from MSCs. In addition, MSCs decreased the expression of genes for the molecules associated with endoplasmic reticulum stress Atf4, Bip, and p21, which are associated with apoptosis. The results show that MSCs inhibit the expression of proapoptotic genes and decrease the number of apoptotic cells in the damaged corneas, and this action might be one of the mechanisms of the therapeutic action of MSCs.

Assessment of the Effect of Infliximab on Immunomodulation Properties of Mesenchymal Stem Cells In Vitro.

Purpose: Mesenchymal stem cells (MSCs) have immunomodulatory traits making them a promising choice in the treatment of inflammatory diseases such as graft-versus-host disease (GVHD). Tumor necrosis factor-alpha (TNFα) is a major player of inflammatory disease which is blocked by infliximab to reduce the inflammation. The present study aims to assess the infliximab effects on the anti-inflammatory properties of MSCs. Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs) were co-cultured with peripheral blood mononuclear cells (PBMCs) of GVHD patients in the presence of 10, 20 and 30 µg/mL of infliximab for 48 and 72 hours. The mRNA expression of indoleamine-2,3- dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), as well as the secreted amount of prostaglandin E2 (PGE2) in the culture supernatant, were examined. Results: The results of this study show that the expression of IDO and iNOS genes, as well as the secretion amount of PGE2 in co-cultured groups raised dramatically, compared to the culture of BMMSCs or PBMCs alone. In co-culture groups containing infliximab, the expression of IDO and iNOS and also the amount of released PGE2 was significantly decreased compared to the control group without infliximab. However, no difference was found in the expression of assayed factors between 48 and 72 hours of treatments. Conclusion: As an anti-TNFα agent, infliximab can decrease the inflammation in the microenvironment of MSCs, which might mitigate the immunomodulatory effects of MSCs. These effects of anti-inflammatory agents on the immunomodulatory capacity of MSCs should be considered in MSC therapy.

Mesenchymal Stem Cell-Mediated Immuno-Modulatory and Anti- Inflammatory Mechanisms in Immune and Allergic Disorders.

Background: Mesenchymal Stem Cells (MSCs) are present in almost all the tissues of the body and act as the backbone of the internal tissue homeostasis. Among their various characteristic features, immuno-modulatory and/ anti-inflammatory properties play an important role in therapeutics.Objective: The current topic focuses on the characterization and immuno-modulatory and/ anti-inflammatory properties of MSCs. To present and discuss the current status of MSCs immuno-modulatory properties.Methods: Available literature on MSCs properties and patents have been detailed, critically interpreted, and discussed based upon available literature. The main focus has been on their characteristic immuno-modulatory and anti-inflammatory properties though some of the basic characterization markers have also been detailed. The databases searched for the literature include PubMed, Med Line, PubMed Central, Science Direct and a few other scientific databases.Results: MSCs are present in a very limited concentration in the tissues, and as such their culture expansion becomes imperative. MSCs immuno-modulatory and anti-inflammatory roles are achieved through direct cell-cell contact and / by the release of certain factors. Such properties are controlled by micro-environment upon which currently very limited control can be exerted. Besides, further insights in the xeno-protein free culture media as against the fetal bovine serum is required.Conclusion: MSCs have been well-isolated, cultured and characterized from numerous tissues of the body. The majority of the studies have shown MSCs as immuno-compromised with immunomodulatory and / or anti-inflammatory properties except some of the latest studies that have failed to achieve the desired results and thus, demand further research. Further research is required in the area to translate the results into clinical application.

Immunosuppressive effects of mesenchymal stem cells on tacrolimus therapy in rat heart transplant model

Introduction: Mesenchymal stem cells (MSCs) are used in various clinical settings for effective cell therapy by taking advantage of their immunomodulatory, regenerative, and anti-inflammatory properties. We previously investigated the effects of the regenerative and anti-inflammatory properties of MSCs for consideration of their clinical application in organ transplantation. Since immunosuppressant agents are administered in nearly all clinical cases of organ transplantation, clarification of the immunological interaction between MSCs and the calcineurin inhibitor tacrolimus (TAC) is needed.Aim: Due to potential use of MSCs in organ transplantation, we assessed immunological interactions between TAC and MSCs in vivo.Methods: Adipose tissue-derived MSCs (AT-MSCs) were obtained from wild-type Lewis rats. We then used a rat heart transplantation model to observe the immunosuppressive effects of AT-MSCs, TAC, and those in combination. Following allogeneic heterotopic heart transplantation from ACI rats to Lewis rats, graft survival was assessed in groups treated with AT-MSCs, TAC, both, or neither.Results: Median survival of the allograft was 14.5 days in the TAC-alone group and 11 days in the MSC+TAC group. Although the difference between those groups was not significant, the survival periods of both were significantly longer as compared to that of the control (median survival =5 days, P<0.05) and MSC-alone (median survival =5 days, P<0.05) groups.Conclusions: Administration of AT-MSCs did not decrease the beneficial immunosuppressive effect of TAC on heart graft survival. TAC appears to be compatible and effective for clinical use as an immunosuppressant with AT-MSCs.

Effects of Human Adipose-Tissue Derived Stem Cell Infusion on the Immunological Consequences in Skin Allograft Mice

Background: Many in vitro experiments have demonstrated the immunosuppressive properties of mesenchymal stem cells (MSCs). However, such properties have not yet been fully established in an in vivo setting. The purpose of this study was to determine immunosuppressive and anti-inflammatory properties of MSCs in a preclinical animal model in order to pave the way for replacement of conventional immunosuppressive therapy.