Novel approaches to lupus drug discovery using stem cell therapy. Role of mesenchymal-stem-cell-secreted factors

Introduction: Patients with systemic lupus erythematosus (SLE) are at increased risk for premature death, particularly among young adults, and present dilemmas regarding drug efficacy versus toxicity. Novel therapeutic strategies have included the use of mesenchymal stem cell (MSC) therapies that are promising but still have limitations. In several disease models, it has become apparent that MSCs do not necessarily replace diseased tissues but rather exert complex paracrine effects that are mediated by their extracellular-secreted products. Areas covered: In this review, the authors highlight the data on MSC treatment of SLE and related mechanisms of actions. This data includes the recent evidence that MSC-secreted factors such as extracellular microvesicles (MVs) are important mediators of MSC therapy. Among MVs, the authors delineate the role of exosomes as triggers of regenerative effects in target cells, mediated by transfer of proteins, mRNAs or microRNAs. The authors also outline some of the biological and regulatory restraints encountered by MSC therapy, in contrast to the potential advantages of MSC-derived exosomes as new therapeutic tools in SLE. Expert opinion: There is concern about reproducible data on the use of MSC therapy in rheumatic diseases and specifically SLE. Although most experts consider MSCs to be safe, there are still worries over donor variability, immune-mediated rejection, culture-induced senescence, loss of functional properties and genetic instability or eventual malignant transformation. MSC-released factors could avoid most limiting factors associated with cell therapy and are therefore expected to provide a new and safe therapeutic option at an affordable cost.