Abstract:Recently, mesenchymal stem/stromal cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of inflammatory bowel disease (IBD), given their immunoregulatory and pro-survival attributes. MSCs alleviate dysregulated inflammatory responses through the secretion of a myriad of anti-inflammatory mediators, such as interleukin 10 (IL-10), transforming growth factor-β (TGFβ), prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene-6 (TSG-6), etc. Indeed, MSC treatment of IBD is large… Show more
“…81,82 The safety and short-term efficacy of MSCs administration has been demonstrated, and the potential challenges associated with the treatment of MSCs are slowly being addressed. 83,84 Application of MSCs exhibits distinct mechanisms of action compared to conventional drug interventions, as shown in Table 1. Firstly, MSCs can selectively migrate to damaged intestinal tissues through homing effects and replace damaged tissues.…”
Section: Current Treatments For Ibd Including Mscsmentioning
confidence: 99%
“… 81 , 82 The safety and short-term efficacy of MSCs administration has been demonstrated, and the potential challenges associated with the treatment of MSCs are slowly being addressed. 83 , 84 Figure 2 Different origins of MSCs possess self-renewal effect enabling allogeneic and autologous cell therapy. MSCs of different origins treat diseases through their broad differentiation potential.…”
Section: Current Treatments For Ibd Including Mscsmentioning
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.
“…81,82 The safety and short-term efficacy of MSCs administration has been demonstrated, and the potential challenges associated with the treatment of MSCs are slowly being addressed. 83,84 Application of MSCs exhibits distinct mechanisms of action compared to conventional drug interventions, as shown in Table 1. Firstly, MSCs can selectively migrate to damaged intestinal tissues through homing effects and replace damaged tissues.…”
Section: Current Treatments For Ibd Including Mscsmentioning
confidence: 99%
“… 81 , 82 The safety and short-term efficacy of MSCs administration has been demonstrated, and the potential challenges associated with the treatment of MSCs are slowly being addressed. 83 , 84 Figure 2 Different origins of MSCs possess self-renewal effect enabling allogeneic and autologous cell therapy. MSCs of different origins treat diseases through their broad differentiation potential.…”
Section: Current Treatments For Ibd Including Mscsmentioning
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.
“…Consequently, the attenuation of the inflammatory response improves the structure of the colonic wall in mice, reduces the abundance of pro-inflammatory bacteria such as Akkermansia muciniphila and Escherichia coli , and ultimately restores the homeostasis of gut microbiota [ 40 ]. Recent studies have shown that MSC-derived EVs can improve the composition of the gut microbiota by significantly elevating OTU abundance and mitigating colitis-induced decrease in α-diversity while increasing the percentage of beneficial intestinal bacteria and counteracting the deleterious function of disease-associated bacteria [ 85 ]. The administration of EVs secreted by embryonic MSCs can reduce the presence of lipopolysaccharide [ 86 ] in the intestine and increase gut microbiota SCFAs, a mechanism which effectively prevents the impairment of intestinal barrier function caused by LPS and indirectly diminishes the recruitment of adipose tissue macrophages (ATM) triggered by LPS [ 87 ].…”
Section: Microbiota Involved In and Beyond The Intestinementioning
The intestinal ecological environment plays a crucial role in nutrient absorption and overall well-being. In recent years, research has focused on the effects of extracellular vesicles (EVs) in both physiological and pathological conditions of the intestine. The intestine does not only consume EVs from exogenous foods, but also those from other endogenous tissues and cells, and even from the gut microbiota. The alteration of conditions in the intestine and the intestinal microbiota subsequently gives rise to changes in other organs and systems, including the central nervous system (CNS), namely the microbiome–gut–brain axis, which also exhibits a significant involvement of EVs. This review first gives an overview of the generation and isolation techniques of EVs, and then mainly focuses on elucidating the functions of EVs derived from various origins on the intestine and the intestinal microenvironment, as well as the impacts of an altered intestinal microenvironment on other physiological systems. Lastly, we discuss the role of microbial and cellular EVs in the microbiome–gut–brain axis. This review enhances the understanding of the specific roles of EVs in the gut microenvironment and the central nervous system, thereby promoting more effective treatment strategies for certain associated diseases.
“…They can be isolated from bone marrow, adipose tissue and umbilical cord, and unlike hematopoietic stem cells, they have low immunogenicity [ 168 ] . In clinical trials, MSCT has proven to be safe and effective for the treatment of refractory CD [ 180 - 182 ] and UC [ 183 - 185 ] , although the long-term efficacy of MSCT must yet be verified [ 186 ] .…”
Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a “healthier profile” and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.
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