Mesenchymal (Stem) Stromal Cells Based as New Therapeutic Alternative in Inflammatory Bowel Disease: Basic Mechanisms, Experimental and Clinical Evidence, and Challenges

Abstract

Inflammatory bowel diseases (IBD) are an example of chronic diseases affecting 40% of the population, which involved tissue damage and an inflammatory process not satisfactorily controlled with current therapies. Data suggest that mesenchymal stem cells (MSC) may be a therapeutic option for these processes, and especially for IBD, due to their multifactorial approaches such as anti-inflammatory, anti-oxidative stress, anti-apoptotic, anti-fibrotic, regenerative, angiogenic, anti-tumor, or anti-microbial. However, MSC therapy is associated with important limitations as safety issues, handling difficulties for therapeutic purposes, and high economic cost. MSC-derived secretome products (conditioned medium or extracellular vesicles) are therefore a therapeutic option in IBD as they exhibit similar effects to their parent cells and avoid the issues of cell therapy. In this review, we proposed further studies to choose the ideal tissue source of MSC to treat IBD, the implementation of new standardized production strategies, quality controls and the integration of other technologies, such as hydrogels, which may improve the therapeutic effects of derived-MSC secretome products in IBD.

Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges

“…Additionally, SCs can regulate human cells, acting as cell producers and managers in the body. 15 , 17 However, SCs in vivo are also affected by their local niche and can undergo structural changes, damage, depletion, cancerization, and even death, 20 which can affect their differentiation and secretion functions. SC therapy involves transplanting exogenous SCs into patients with impaired SC structure and function, supplementing, resetting, or transforming their own SCs to repair or replace damaged cells or tissues and cure diseases.…”

“… 13 IBD is characterized by the loss of control of immune cells, damage to intestinal structural cells, and abnormalities of intestinal resident SCs. 14 , 15 Transplantation of SCs can regulate or rebuild immune cells, repair or supplement structural cells, such as intestinal epithelial cells (IECs), and potentially lead to a complete cure of IBD. 16 , 17 This review summarizes recent research on the use of SCs for treating IBD, providing targeted treatment recommendations and research strategies for IBD patients.…”

Biogenesis, Composition and Potential Therapeutic Applications of Mesenchymal Stem Cells Derived Exosomes in Various Diseases

“… 363 Dextran sulphate sodium induced mouse model study suggests that inflammatory responses are significantly controlled by inducing the production of M2 macrophages. 302 , 364 Mice treated with MSC-EVs promote repair and regeneration of damaged epithelial cells by production of higher levels of immunosuppressive factors (IL-10 and TGF-β) and low level of IL-1β, NO, and IL-18 by depressing NF-κB and iN-OS-driven signaling in 2,4,6-trinitrobenzene sulfonic acid induced colitis. 359 , 364 , 365 According to the results of all these findings, MSC-EXOs can act as a significant regulator and novel therapeutic agent by reducing inflammatory responses.…”

“… 302 , 364 Mice treated with MSC-EVs promote repair and regeneration of damaged epithelial cells by production of higher levels of immunosuppressive factors (IL-10 and TGF-β) and low level of IL-1β, NO, and IL-18 by depressing NF-κB and iN-OS-driven signaling in 2,4,6-trinitrobenzene sulfonic acid induced colitis. 359 , 364 , 365 According to the results of all these findings, MSC-EXOs can act as a significant regulator and novel therapeutic agent by reducing inflammatory responses. They can also successfully block immune responses and promote the survival and regeneration of wounded cells.…”

Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis

“…Thus, it is necessary to comprehend how the host immune system reacts to allogenic MSCs and how this may influence the therapeutic efficacy of MSCs in various inflammation models. MSC-based therapies have been developed in the context of inflammation observed in numerous disease models, such as graft versus host disease (GVHD) [ 84 ], inflammatory bowel disease (IBD) [ 85 ], diabetic cardiomyopathy [ 86 ], and many others. In this review, we will discuss some of the fundamentals that link inflammation to different disease models, as well as some of the biological properties of MSCs that can help them be used as a treatment for inflammatory diseases like OA.…”