Background/Purpose: Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that targets multiple organ systems.  Current treatment options for SLE often cause non-specific immune suppression, which can lead to undesirable side effects.  Therefore a new treatment approach with limited harmful side effects, is of particular interest.  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, and have proven successful at suppressing various immune cells.  In this study we examine the efficacy of human MSCs with varying origin on disease in murine based lupus.

Methods: To define the efficacy of human MSCs on murine lupus we harvested MSCs from umbilical cords, healthy donor bone marrow, and lupus patient bone marrow (n=3-4 of each).  At disease onset, 15-17 weeks of age, MRL/lpr mice were intravenously injected with 1×10⁶ MSCs from one of the three MSC origins or PBS.  Urine and blood were collected at 2,4,6 and 8 weeks post transfer to examine urine albumin excretion and anti-dsDNA antibody levels.  Mice were euthanized at 8 weeks post transfer. Kidneys were collected for pathology and immunohistochemistry.  Spleen and bone marrow were harvested to detect presence of plasma cells, B cells, T cells, and Tregs via flow cytometry.

Results:   All mice receiving MSCs from the various sources showed improved survival, increased body weight, and decreased proteinuria compared to untreated controls.  At 8 weeks post MSC transplant, glomerular IgG, but not C3, deposition was significantly decreased in mice receiving umbilical cord and healthy bone marrow MSCs.  However, MSC from lupus patients caused an increase in glomerular C3 and IgG.  Additionally, while the glomerular pathology score was significantly reduced in the umbilical cord and healthy bone marrow mouse groups, there was no change in pathology of the lupus MSC group when compared to PBS control mice.  Although no differences were seen in the percentage of CD4+ or CD8+ T cells between treatment groups, the lupus MSC group 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. 

Conclusion:   Our results indicate that human MSC from various origins all made an impact on the disease severity of lupus prone mice.  However, the inability of the lupus patient MSCs to prevent kidney damage suggests that umbilical cord or healthy donor bone marrow MSCs are more effective as disease modulators in vivo.  These data indicate that MSCs derived from lupus patients are not a strong candidate for therapeutic intervention in lupus.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differential-efficacy-of-human-mesenchymal-stem-cells-on-disease-in-murine-lupus-based-on-source-of-origin/