title: Novel approaches to lupus drug discovery using stem cell therapy. Role of mesenchymal-stem-cell-secreted factors.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Universidad de los Andes, Centro de Investigaciones Biomédicas, Facultad de Medicina , Santiago de , Chile.
authors.forename: Fernando E
authors.initials: FE
authors.lastname: Figueroa
authors.forename: Jimena
authors.initials: J
authors.lastname: Cuenca Moreno
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
mesh_terms: D000818:Animals; D055354:Exosomes / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*