Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice

MSC are being explored as a promising novel treatment for SLE. In this study, we: 1) assessed the differential effects of allogeneic versus syngeneic MSC transplantation on lupus-like disease, 2) explored the mechanisms by which MSC modulate disease, and 3) investigated whether lupus-derived-MSC have intrinsic immunomodulatory defects. We showed that in MRL/lpr mice and (NZB/NZW)F1 mice, both B6-MSC and lupus-MSC from young mice ameliorated SLE-like disease and reduced splenic CD3+CD4 + T lymphocytes and CD19+CD21 + B lymphocytes. However, lupus-MSC from older (NZB/NZW)F1 mice did not reduce spleen weights, glomerular IgG deposits, renal pathology, interstitial inflammation, CD3+CD4 + T lymphocytes or CD19+CD21 + B lymphocytes significantly. Thus MSC transplantation ameliorates SLE-like disease partly through decreasing CD4 + T cell and naïve mature B cell numbers. Allogeneic MSC may be preferred over syngeneic lupus-derived-MSC given the decreased overall effectiveness of post-lupus-derived-MSC, which appears partially due to disease and not exclusively intrinsic defects in the MSC themselves.

► MSC infusion ameliorates lupus in MRL/lpr and NZB/NZW mice. ► MSC from control and predisease mice treat active disease. ► MSC from diseased mice are not as effective in treating disease. ► Nitric oxide expression is higher in MSC from control mice. ► Inhibiting T cell proliferation correlated with clinical effect.