Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Allogenic Mesenchymal Stem Cell Transplantation Ameliorates Lupus Mice Via Inhibition of B-Cell Activating Factor (BAFF)
Sun1, Lingyun, Ma1, Xiaolei, Zhang1, Huayong, Gu1, Zhifeng, Silver2, Richard M., Gilkeson2, GS
B cells play an important role in the pathogenesis of SLE. B-cell activating factor (BAFF) is a member of the TNF superfamily that regulates B-cell survival and autoreactivity. Recent evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs) possess immunosuppressive properties both in vitro and in vivo. We previously demonstrated that transplantation of human MSCs can significantly improve the autoimmune disorders in MRL/lpr mice. This study investigates whether effect and mechanism of murine BM-MSCs transplantation for MRL/lpr mice occurs by inhibiting B cell activation and BAFF expression.
18-week-old MRL/lpr mice were treated with BM-MSCs derived from BALB/C or saline. The disease-free BALB/C mice were used as negative control. Mice were monitored for 24h proteinuria. Sera were tested for levels of anti-double-stranded DNA (ds-DNA) antibodies, BAFF, IFN-g, IL-2, IL-4, IL-10 and TGF-b. Mice were sacrificed at 26 weeks of age, and kidneys were subjected to histologic examination. The percentage and number of marginal zone (MZ), T1 and T2 B cells in spleen were detected by flow cytometry.
MSCT prevented disease onset and significantly prolonged survival. The treated mice had significantly less renal damage. Eight weeks after transplantation, the levels of BAFF in serum in treated group decreased significantly than in placebo as well as the levels of serum IFN-g and IL-10, while the levels of serum TGF-b were increased. Treated mice had significantly smaller spleens than control animals, with fewer MZ, T1, T2 and activated B cells.
Our findings suggest that MSCT can inhibit the excessive activation of B cells in MRL/lpr mice, including T1, T2 and MZ B cells. BAFF production was reduced in MSCs-treated mice in association with the diminished production of anti-dsDNA autoantibodies, proteinuria, IFN-g and IL-10. Thus, down-regulation of BAFF may play an important role in the mechanism of action by which MSCT ameliorates lupus progression.
To cite this abstract, please use the following information:
Sun, Lingyun, Ma, Xiaolei, Zhang, Huayong, Gu, Zhifeng, Silver, Richard M., Gilkeson, GS; Allogenic Mesenchymal Stem Cell Transplantation Ameliorates Lupus Mice Via Inhibition of B-Cell Activating Factor (BAFF) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1046