Differential efficacy of human mesenchymal stem cells on disease in murine lupus based on source of origin. (P4162)

Abstract

Abstract Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that targets multiple organ systems. A population of non-hematopoetic stem cells, mesenchymal stem cells (MSC), are of increasing interest as a therapeutic option for autoimmune diseases such as SLE. MSCs can be derived from various sources such as bone marrow or umbilical cords. In this study we examine the efficacy of human MSCs with varying origin on disease in murine based lupus. Human MSCs were harvested from umbilical cords, healthy donor bone marrow, and lupus patient bone marrow. We showed that in MRL/lpr mice, MSCs from all sources improved survival, increased body weight, and decreased proteinuria. Glomerular IgG, but not C3, deposition is significantly decreased in mice receiving umbilical cord and healthy donor MSCs. However, MSC from lupus patients caused a significant increase in glomerular C3 and IgG. Although no differences were seen in the percentage of CD4+ or CD8+ T, mice receiving lupus MSCs experienced a 2-fold increase in the percentage of Foxp3+ cells in the spleen. These mice also experienced this percentage increase in TCRβ+, B220+, and CD138+ cells in the bone marrow. Human MSC from various origins all made an impact on the disease severity of lupus prone mice. However, these results suggest that MSCs from healthy donors or umbilical cords appear to be more effective in murine lupus than the MSCs derived from lupus patients.