“…Using the 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis mouse model, it has been shown that MSCs are capable of expanding the existing Tr1 pool. However, co-expression of CD44 and IL-10 was used to define these putative Tr1 cells while the presence of both CD49b and LAG-3 was not shown ( 113 ).…”
Section: Tr1 Cells and Tolerance In Autoimmune Disease Settingsmentioning
Type 1 regulatory T (Tr1) cells, in addition to other regulatory cells, contribute to immunological tolerance to prevent autoimmunity and excessive inflammation. Tr1 cells arise in the periphery upon antigen stimulation in the presence of tolerogenic antigen presenting cells and secrete large amounts of the immunosuppressive cytokine IL-10. The protective role of Tr1 cells in autoimmune diseases and inflammatory bowel disease has been well established, and this led to the exploration of this population as a potential cell therapy. On the other hand, the role of Tr1 cells in infectious disease is not well characterized, thus raising concern that these tolerogenic cells may cause general immune suppression which would prevent pathogen clearance. In this review, we summarize current literature surrounding Tr1-mediated tolerance and its role in health and disease settings including autoimmunity, inflammatory bowel disease, and infectious diseases.
“…Using the 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis mouse model, it has been shown that MSCs are capable of expanding the existing Tr1 pool. However, co-expression of CD44 and IL-10 was used to define these putative Tr1 cells while the presence of both CD49b and LAG-3 was not shown ( 113 ).…”
Section: Tr1 Cells and Tolerance In Autoimmune Disease Settingsmentioning
Type 1 regulatory T (Tr1) cells, in addition to other regulatory cells, contribute to immunological tolerance to prevent autoimmunity and excessive inflammation. Tr1 cells arise in the periphery upon antigen stimulation in the presence of tolerogenic antigen presenting cells and secrete large amounts of the immunosuppressive cytokine IL-10. The protective role of Tr1 cells in autoimmune diseases and inflammatory bowel disease has been well established, and this led to the exploration of this population as a potential cell therapy. On the other hand, the role of Tr1 cells in infectious disease is not well characterized, thus raising concern that these tolerogenic cells may cause general immune suppression which would prevent pathogen clearance. In this review, we summarize current literature surrounding Tr1-mediated tolerance and its role in health and disease settings including autoimmunity, inflammatory bowel disease, and infectious diseases.
“…In animal models, MSCs have shown promising results in the treatment of inflammatory bowel disease (IBD) [82][83][84] as well as CRC. 24,26 Their therapeutic effects are mediated through either cell-cell contact or paracrine effects.…”
Section: Application Of Mesenchymal Stem Cell-derived Exosomes In Crcmentioning
Colorectal cancer (CRC) is one of the main causes of cancer‐related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer‐related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell–cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell‐free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC‐derived exosomes for possible cell‐free therapy in CRC.
“…For example, MSCs are involved in immune regulation, acting on immune cells, recruiting Treg lymphocytes and reducing Th1, Th17 and B cell differentiation to treat IBD. 156 Similarly, it has also been extensively studied in refractory systemic lupus erythematosus, 157 graft-versus-host disease 158 and rheumatoid arthritis. 159 Figure 4 Immunomodulatory mechanisms of MSCs in the treatment of IBD.…”
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.
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