Umbilical cord-derived stromal cell therapy for rheumatoid arthritis: what does the future hold?

Abstract

Limitations of the current therapies for rheumatoid arthritis Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease characterized by progressive cartilage loss and bone destruction with progressive functional decline. It is thought to be an autoimmune disease with aberrant Band T-cell function eventually culminating in an increased local production of inflammatory mediators and cytokines in particular, such as TNF-a, IL-1b, IL-6 and others. Collectively these cytokines orchestrate the molecular cascades that are activated in osteoclasts, fibroblasts and immune cells that culminate in joint destruction. An appreciation of these pathways has lead to the development of anticytokine therapies, costimulatory pathway blockade therapy and B-cell depletion therapies, which have dramatically improved patient outcomes. Despite these therapeutic advances, it is clear that a significant burden of RA inflammatory disease activity remains suboptimally treated. First, many patients are intolerant to the current therapies. Second, there is the issue of toxicity of existing therapies including the risks of serious infections or other noninfectious immunological perturbations that restrict therapy use. Third, many patients who benefit from the existing therapies only have a partial response and continue to experience significant joint pains owing to joint damage and functional loss. Finally, there is a small hard core of cases that have a fairly resistant inflammatory course where newer approaches are needed. Multipotential stromal cells, also called mesenchymal stem cells (MSCs) were originally studied for their tissue regenerative capabilities. The immunomodulatory capacity of allogeneic MSCs was first documented in a pioneering paper by Le Blanc et al. who showed