Mesenchymal Stem Cell Therapy for Autoimmune Disease: Risks and Rewards

Abstract

Mesenchymal stem cells (MSC) possess a range of immunomodulatory properties which they exert through soluble mediators and through direct cell-cell contact. Due to these immune regulatory properties, the safety and clinical efficacy of MSC treatment has been tested in a number of autoimmune disorders. In this review we analyze the current data from early phase trials into Crohn's disease, systemic lupus erythematosus, and rheumatoid arthritis. In general, no adverse side effects were observed in patients treated with MSC; however, their clinical efficacy is difficult to interpret. Systemic or site-specific administration of MSC has been reported to exert potent immunomodulatory effects in 7 of the 11 trials discussed. Nonetheless, the mechanism(s) by which MSC exert their regulatory effects in vivo remain largely unknown. We discuss potential limitations or safety concerns associated with MSC therapy, including the heterogeneity of MSC and their potential contribution to disease pathogenesis, which need to be considered when designing future clinical trials, along with the need to standardize trial design. Although we are bridging the translational gap between scientific observations on MSC function and clinical applications for therapy, our understanding of basic MSC biology is still limited. Despite these issues, large, double-blinded, multicenter clinical trials are already underway. Further research into the endogenous function of MSC is required to elucidate the mechanism by which therapeutic MSC are acting.

Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal Stem Cell Infusion on Osteopenia

“…Previous findings have pointed out that recipient immunological components, particularly T lymphocytes and inflammatory cytokines TNF-α and Interferon-gamma, actively respond to the transplanted MSCs and initiate the immunomodulatory function of donor MSCs 18, 19, 71. However, conflicting results still exist regarding therapeutic effects of MSCs on immune disorders 72; specifically, MSC transplantation could be conditionally therapeutic depending on recipient micro-environmental alterations 14, 17, but detailed investigations of how the diseased recipient micro-milieu affects the donor MSC function are lacking. In this study, we for the first time uncovered that recipient diabetes mellitus impairs MSC-mediated therapy and immunomodulation, despite the onset of inflammation observed here and reported previously 37.…”

Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

“…However, Exofree from MSCs as well as the digestion assay of uMSC-Exo with proteinase K largely diminished the possibility of soluble factors in the supernatant of uMSC or protein components in uMSC-Exo to be the major elements with anti-HCV potency. Until now, MSC treatments have caused slight or no adverse reactions in clinical trials [51,52].…”

Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Are Functionally and Genetically Different From Bone Marrow-Derived Mesenchymal Stromal Cells

“…This has arisen because of the strong interest in the research and therapeutic use of these cells. MSCs are multipotent cells which have been extensively tested as therapeutic agents for the treatment of degenerative diseases, autoimmune disorders and wound repair . In addition, the cells can be used to model human diseases, for example, musculoskeletal disorders and nonhematological mesenchymal cancers .…”