Related Experiment Video
Updated: May 7, 2026
The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
A novel trained mesenchymal stromal cell-based therapy, HXB-319, effectively controls progressive glomerulonephritis
Hulya Bukulmez1, Adrienne Dennis1, Jane Reese2
1Division of Pediatric Rheumatology, Department of Pediatrics, Metrohealth Medical Center, Case Western Reserve University, Cleveland, 44109, OH, United States.
Introduction:
Systemic lupus erythematosus (SLE) is driven by abnormal type-I and -II interferon activation, affecting a variety of immunocompetent cells. Mesenchymal stromal cells (MSCs) can modulate inflammation but often lack consistent potency. We developed HXB-319, an MSC-based therapy targeting inflammatory pathways in SLE. Previously, HXB-319 was shown to reduce alveolar hemorrhage in an SLE model. Here, we report its effects in a model of SLE that progresses to end stage kidney disease.
Materials And Methods:
SLE-like disease was induced via intraperitoneal (IP) pristane injection in female BALB/cJ mice, followed by treatment with naïve MSCs or HXB-319. Over 9 months, survival and proteinuria were monitored. Upon euthanasia, kidneys were analyzed for histopathology and gene expression, splenocytes for immune subsets by flow cytometry, and serum for autoantibodies, growth factors, and cytokines.
Results:
HXB-319 significantly altered plasmacytoid dendritic cells, CD4+PD-L1+ cells, and both CD4+ and CD8+ RORγt+ (Th17 cells) subsets. HXB-310 lowered IFN-γ (P < 0.001), IL-17A (P = 0.01), BAFF (P < 0.05), and anti-dsDNA (P < 0.05), compared to untreated mice. HXB-319, but not naïve MSCs, significantly improved survival, halted progression of kidney disease, and stabilized proteinuria (all P < 0.05).
Conclusion:
HXB-319 demonstrates potential for mitigating SLE-associated glomerulonephritis, improving survival, and reducing proteinuria and glomerulosclerosis.
