Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

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 largely carried out through local microcirculation construction, colonization and repair, and immunomodulation, thus alleviating diseases severity. The clinical therapeutic efficacy relies on to the marked secretion of various secretory molecules from viable MSCs via paracrine mechanisms that are required for gut immuno-microbiota regulation and the proliferation and differentiation of surrounding cells like intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). For example, MSCs can induce IECs proliferation and upregulate the expression of tight junction (TJs)-associated protein, ensuring intestinal barrier integrity. Concerning the encouraging results derived from animal studies, various clinical trials are conducted or ongoing to address the safety and efficacy of MSCs administration in IBD patients. Although the safety and short-term efficacy of MSCs administration have been evinced, the long-term efficacy of MSCs transplantation has not yet been verified. Herein, we have emphasized the illumination of the therapeutic capacity of MSCs therapy, including naïve MSCs, preconditioned MSCs, and also MSCs-derived exosomes, to alleviate IBD severity in experimental models. Also, a brief overview of published clinical trials in IBD patients has been delivered.

Keywords: Cytokines; Inflammation; Inflammatory bowel disease (IBD); Intestinal integrity; Mesenchymal stem/stromal cells (MSCs).

Fig. 1

The IBD pathogenesis. The interactions between environmental factors, genetic susceptibility, and microbial flora may perturb intestinal hemostasis and thus induce the transduction of dysregulated immune responses and underlie resultant tissue damage. Inflammatory bowel diseases (IBD), innate lymphoid cells (ILC), T helper cell (Th), interleukin (IL), transforming growth factor-beta (TGF-β), regulatory B cells (Bregs), regulatory T cells (Tregs), regulatory dendritic cells (rDCs), natural killer T (NKT) cells, tumor necrosis factor α (TNFα)

Fig. 2

Underlying mechanisms behind the immunomodulatory attributes of MSCs

Fig. 3

Clinical trials based on MSCs therapy in IBD conditions registered on https://clinicaltrials.gov (June 2022). The schematic exhibits the clinical studies in the light of cell source (A), cell type (B), administration route (C), condition (D), study phase (E), and study location (F). Inflammatory bowel diseases (IBD), mesenchymal stem/stromal cell (MSC), bone marrow (BM), umbilical cord (UC), adipose tissue (AT), Wharton's jelly (WJ), Crohn's disease (CD), ulcerative colitis (UC), not applicable (NA)