Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A Review of What We Know So Far

Abstract

Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis. Newer, yet unproven, cellular therapies include allogeneic mesenchymal stromal cells, which have been shown to be effective in graft‐versus‐host disease and in healing Crohn's fistulas. Chimeric antigen receptor T cells are effective in various malignancies, with possible application in rheumatic diseases, as shown in preclinical studies in murine lupus and recently in human lupus. Treg cells are one of the master controllers of the immune response and are decreased in number and/or effectiveness in specific autoimmune diseases. Expansion of autologous Treg cells is an attractive approach to controlling autoimmunity. There are a number of other regulatory cells in the immune system, including Breg cells, dendritic cells, macrophages, and other T cell types, that are in early stages of development as treatments. In this review, the current evidence for the efficacy and mechanisms of actions of cellular therapies already in use or in clinical trials in human autoimmune diseases will be discussed, including the limitations of these therapies and potential side effects.

Comparison of therapeutic effects of mesenchymal stem cells from umbilical cord and bone marrow in the treatment of type 1 diabetes

“…The underlying mechanism is mainly associated with modulating autoimmune responses against islets. In addition to suppressing pathogenic CD8 + T cells, T helper 1 (Th1) cells and T helper 17 (Th17) cells [ 9 , 10 ], MSCs can also promote regulatory T cells (Tregs) through paracrine effects, direct cell receptor interactions or mitochondrial transfer [ 11 , 12 ]. Because islets are highly vascularized mini-organs, the promotion of angiogenesis by MSCs in islets is another potential mechanism in T1D [ 13 , 14 ].…”

Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002–2021)

“…However, several animal experiments have shown that MSCs may increase the risk of cancer by inhibiting the function of CD8 + T cells (75)(76)(77). Besides, most of the relevant clinical trials are not unblinded, and the number of patients included is small (N<110) (78). There is currently no large multicenter placebocontrolled trials, so the efficacy and safety of MSCs in the treatment of AIDs needs to be further confirmed (78).…”

“…Besides, most of the relevant clinical trials are not unblinded, and the number of patients included is small (N<110) (78). There is currently no large multicenter placebocontrolled trials, so the efficacy and safety of MSCs in the treatment of AIDs needs to be further confirmed (78). MSCderived exosomes (MSC-Exos) have biological functions similar to MSCs, but MSC-Exos are more stable and less toxic, which can largely avoid the body's triggering immune response and capillary embolism and other adverse events, so researchers are actively exploring the strategy of MSCs-Exos in the treatment of AIDs (4,10,79).…”

Editorial: Stem cell transplantation in autoimmune diseases (AID)

“…As to alternative cellular treatment options for AID, CAR-Tcells have already been used in systemic lupus erythematosus with seemingly good benefit (6), and clinical studies on mesenchymal stem cells (MSC) dating back to the 90-ies held promise yet (7). Nevertheless, adequately powered controlled trials with MSC have not been published, and their mechanism of action remains unclear in parts.…”