Crosstalk between mesenchymal stem cells and macrophages in inflammatory bowel disease and associated colorectal cancer

Abstract

Mesenchymal stem cells (MSCs) are attractive seed cells for immunotherapy, tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities, diverse immunoregulatory functions and ease of isolation from a wide range of tissues. MSCs exert their immunoregulatory effect on immune cells via cell-to-cell contact and paracrine mechanisms. In turn, MSCs can also be modulated by immune cells. Macrophages are constantly present in the mucosa of the intestinal tract of mammals and play an important role in the development and progression of inflammatory bowel disease (IBD), a chronic and recurrent inflammatory disease of the gastrointestinal tract characterized by idiopathic mucosal inflammation. The increased morbidity and mortality of IBD have made it a disease hard to cure in the clinic. MSCs have emerged as an important tool for IBD therapy due to their abilities to differentiate into enterocyte-like cells and regulate inflammatory cells, especially macrophages. In this review, we discuss the recent advances in the interaction between MSCs and macrophages in diseases, with an emphasis on IBD. We propose that an optimized MSC-based therapy would provide a novel strategy for the treatment of IBD and the prevention of IBD-associated colorectal cancer (CRC).

Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment

“…Our results further suggest that when IFN-γ priming of MSCs is followed with exposure to inflammatory macrophages, the enhanced immunomodulation is maintained. This is important because there is opposing evidence of crosstalk between MSC and macrophages in wound repair and cancer studies [ 42 – 44 ], which results in altered phenotype and function. Inflammatory licensing with poly I:C resulted in only modest improvement in MSC immunomodulatory function and gene expression changes compared to that observed with IFN-γ stimulation.…”

Mesenchymal Stromal Cells Directly Promote Inflammation by Canonical NLRP3 and Non-canonical Caspase-11 Inflammasomes

“…Therefore, MSCs have attracted great interest for clinical application in treating various inflammatory diseases. Some studies have already demonstrated the beneficial effects of MSCs in ameliorating various inflammatory disorders, including sepsis, inflammatory bowel disease and experimental allergy encephalomyelitis [ 7 , 8 , 27 , 29 ]. However, therapeutic effects were not always achieved [ 8 , 26 , 29 ].…”

Exosome‐mediated effects and applications in inflammatory bowel disease

“…Thus, stem cell-derived exosomes have demonstrated significant therapeutic benefits in several diseases. Mao et al (2017a) showed that mesenchymal stem cell (MSC)-derived exosomes could relieve the symptoms of IBD and helped in the recovery of damaged tissues and organs.…”