Background Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by a chronic course and variable severity; despite recent diagnostic and therapeutic advances, the management of the disease remains a clinical challenge in patients refractory to conventional treatments. Recently, mesenchymal stromal cells (MSCs) have emerged as a new potential therapeutic option in SLE.
However, there is still a lack of convincing data confirming their efficacy and safety. Single case reports and small patient series have reported positive and negative outcomes in very complex and different clinical settings (i.e. multiple organ involvement and multiple concomitant therapies).
These controversial results underlined the need for a better understanding of the mechanisms by which MSCs transplant might interact with the host immune system during the different disease stages and induce, at the end, a therapeutic effect.
Objectives to study the therapeutic effect of allogenic MSCs transplantation in a murine model of SLE with particular regard to renal manifestations
Methods Eighty female New Zealand Black/New Zealand White F1 (NZ) mice have been used as model of SLE and C57BL/6J mice have been used as donors of allogenic bone marrow derived MSCs (BMMSCs).
NZ were randomized into the following 4 experimental arms (20 animals each): three groups to be treated at different disease stages (20 weeks-A, 24weeks-B, and 32 weeks-C) with a single intravenous infusion (via caudal vein) of 1x106 cells/kg body weight of allogenic BMMSCs in a saline suspension and a placebo arm (P). As renal biomarkers, 24hours proteinuria was weekly monitored with albustick and serum anti-dsDNA titers at serial sacrifices were evaluated with a commercial ELISA kit.
Results In untreated mice (P), proteinuria tended to became detectable at 20 weeks of age (0.72±0.41mg/day) and further increased until to reach a plateau after 30 weeks of age (3.8±0.77 mg).
In A, a significant decline in proteinuria was observed after treatment; at 24 weeks the mean proteinuria was 0.33±022 which was significantly lower than P at the same age (0.89±0.2; p=0.001); thereafter proteinuria started to increase one month after transplantation reaching similar level of P at 30 weeks of age. Similarly, in B the BMMSCs infusion was followed by significant decline in proteinuria which was maintained for one month (at 28 weeks mean proteinuria 0,252±0,26 vs 1,8±0,77 in P, p=0.03).
In C, no significant effect on proteinuria was observed after treatment.
In P anti dsDNA became firstly detectable since 12 weeks of age but at 18 weeks a substantial positivity was recorded. Both in A,B and C mice, no significant differences in DNA titers have been found after treatments.
Conclusions our data showed that allogenic BMMSCs infusion is effective in reducing proteinuria in this mouse model of SLE if administered early during the disease curse (20 and 24 weeks of age), moreover, the effect is transient lasting for a mean of one month. No effect on autoantibodies production was observed.
This observation might suggest a beneficial effect of BMMSCs transplantation on the inflammatory process at the tissue level rather than a systemic immunomodulation.
Disclosure of Interest : None declared