Background In recent decades, cell-based therapies have emerged as a new therapeutic option for refractory and severe systemic lupus erythematosus (SLE) (1). Mesenchymal stromal cells (MSCs) could represent an excellent candidate but several aspects remain to be extensively investigated such as the most efficient treatment timing and dosage.
Objectives The present research is aimed at comparing the effect of different protocols of allogenic MSCs infusions on clinical and serological parameters in a mouse model of SLE.
Methods 35 female New Zealand Black/New Zealand White F1 (NZB/W) mice have been used as model of SLE and 10 C57BL/6J mice have been used as donors of allogenic bone marrow derived MSCs (BMMSCs). NZB/W mouse were divided into the following experimental groups:
– 5 NZB/W treated with a single MSCs infusion at 20 weeks of age (NZB/W20)
– 5 NZB/W treated with a single MSCs infusion at 24 weeks of age (NZB/W24)
– 5 NZB/W treated with a single MSCs infusion at 32 weeks of age (NZB/W32)
– 5 NZB/W treated with multiple MSCs infusions started at 20 weeks of age (NZB/WM20)
– 5 NZB/W treated with multiple MSCs infusions started at 24 weeks of age (NZB/WM24)
– 10 NZB/W mouse not treated as Controls (C)
Proteinuria was recorded weekly and peripheral blood serum samples were collected at sacrifice to test for anti-dsDNA antibodies (Alpha Diagnostics International). At sacrifice, kidneys were harvested and sections were stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). H&E and PAS stained sections were evaluated for glomerular, interstitial and vascular lesions according to a modified score described by Tao X et al (2).
Results In untreated mice (C) proteinuria was detectable at 17 weeks of age (3.5±2.7 mg/day) and further increased until 35 weeks of age (12.5±3.5 mg/day). At 24 weeks, proteinuria was 1.8±2.3 mg/day in C group, 0.9±0.4 mg/day in NZB/W20, 0.7±0.5 mg/day in NZB/WM20.
At 30 weeks proteinuria was 4.9±2 mg/day in untreated mice, 4.6±5 mg/day in NZB/W20, 3.2±0.2 mg/day in NZB/W24, 0.7±0.5 mg/day in NZB/WM20 and 0.8±0.4 mg/day in NZB/WM24. At 36 weeks proteinuria was 12.5±3.5 mg/day in C group, 8.5+6.1 mg/day in NZB/W20, 3.7+3.4 mg/day in NZB/W24, 9.4+5.1 mg/day in NZB/W32, 6.5±5 mg/day in NZB/WM20 (p=0.006 vs C group) and 4.5+2.5 mg/day in NZB/WM24 (P<0.0001 vs C group).
The titers of the anti-dsDNA antibody did not change between groups. No significant differences in histological kidney scores were observed between single and multiple treatments.
Conclusions Our results showed that multiple MSCs infusion are associated with a decrease of proteinuria; on the contrary both single and multiple treatments had no effect on autoantibodies production as well as on histological progression of the kidney disease.
Hugle T et al. stem cell transplantation for rheumatic autoimmune diseases. Arthritis Res Ther, 2008.
Tao X et al. Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordii Hook F on nephritis in NZB/W F1 mice. Arthritis ResTher, 2006.
Disclosure of Interest None declared