Immunomodulatory effect of multipotent stromal cells

Multipotent stromal (stem) cells are currently the subject of extensive research. Initially, special attention was given to their reparative properties; however, in recent years, the focus switched toward their immunomodulatory effects. Multipotent cells inhibit T cell proliferation (directly and via exosomes), suppress proinflammatory cytokine production, and activate anti-inflammatory cytokine synthesis. Owing to these effects, cell technologies are currently used in the treatment of Huntington disease, multiple sclerosis, autoimmune encephalomyelitis, scleroderma, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, and other disorders. Furthermore, multipotent stromal cells have demonstrated efficacy in acute respiratory distress syndrome models, supporting their potential use in the treatment of COVID-19 complications. They interact with target cells via both paracrine signaling and direct cell–cell interactions. However, multipotent cell-driven immunoregulation and immunosuppression mechanisms are still poorly understood. The use of multipotent cells is highly dependent on the cell source and their functions in vivo; moreover, functional capabilities of stem cells are known to decline with age. It is also essential to consider potential complications of immunomodulatory effects of multipotent stromal cells, including long-term, severe immunosuppression, which may result in prolonged inflammation in infections and facilitate the progression of malignant neoplasms. For the effective use of multipotent cells, changes in gene expression induced by cell culture and various disorders must be taken into account. Further research is warranted into the mechanisms behind the immunomodulatory effect of multipotent stromal cells, as well as indications and contraindications for cell therapy in humans and animals. Moreover, it will be beneficial to investigate ways to control the functions of stem cells in various microenvironments.