Mesenchymal stem cells and their therapeutic applications in inflammatory bowel disease

Abstract

Mesenchymal stem or stromal cells (MSCs) are non-hematopoietic stem cells that facilitate tissue regeneration through mechanisms involving self-renewal and differentiation, supporting angiogenesis and tissue cell survival, and limiting inflammation. MSCs were originally identified and expanded in long-term cultures of cells from bone marrow and other organs; and their native identity was recently confined into pericytes and adventitial cells in vascularized tissue. The multipotency, as well as the trophic and immunosuppressive effects, of MSCs have prompted the rapid development of clinical applications for many diseases involving tissue inflammation and immune disorders, including inflammatory bowel disease. Although standard criteria have been established to define MSCs, their therapeutic efficacy has varied significantly among studies due to their natural heterogenicity. Thus, understanding the biological and immunological features of MSCs is critical to standardize and optimize MSCs-based therapy. In this review, we highlight the cellular and molecular mechanisms involved in MSCs-mediated tissue repair and immunosuppression. We also provide an update on the current development of MSCs-based clinical trials, with a detailed discussion of MSC-based cell therapy in inflammatory bowel disease.

Keywords: cell therapy; inflammatory bowel disease; mesenchymal stem cell; pericyte; tissue repair.

Figure 1. Schematic demonstration of the diverse mechanisms involved in MSCs-mediated tissue repair

A. Self-renewal and multipotent differentiation. B. Tissue migration and repair or replacement of damaged tissue cells. C. Cell contact-dependent immunosuppressive functions via surface molecules. D. Immunotolerance and angiogenesis mediated by secretion of soluble factors. E. Transfer of molecules or organelles by EVs or tunneling nanotubes (TNTs). All the demonstrated MSCs-mediated functions can be modulated by bioactive or inflammatory reagents, such as nitric oxide, IFN-γ, and TNF-α.

Figure 2. MSCs-based clinical trials on clinicaltrials.gov

A. Number of registered clinical trials of MSCs-based therapy from 2004 to 2016 (as of December 25, 2016). B. Distribution of ongoing MSCs-based therapy by disease category. C. Distribution of ongoing MSCs-based therapy by selected common diseases.