Kallikrein gene modified mesenchymal stem cell transplantation protected mice from anti-GBM induced and lupus nephritis (107.10)

Abstract

Abstract Mesenchymal stem cells (MSC) have been reported to be an attractive cell source for treatment of renal diseases. Recently, we reported that kallikreins (klk) play renoprotective role in anti-GBM-induced and lupus nephritis. Here, we investigated whether MSCs could be used as vehicle to deliver klks into injured kidneys and play synergetic protective role against experimental glomerulonephritis. Human KLK1 gene was incorporated into genome of mouse bone marrow-derived MSCs via retroviral vector pMSCV and a stable cell line, hKLK1-MSC, was established and proved to express high level hKLK1. NZW mice with anti-GBM induced nephritis were injected with 105 hKLK1-MSCs (i.v.) and hKLK1 expression was detected from blood and kidneys 2 weeks after injection. Comparing with MSCs injected mice, the hKLK1-MSCs treated mice showed significantly reduced proteinuria (0.188 mg/24 h vs. 0.766 mg/24 h, p<0.05), serum BUN (5.9 mg/dl vs. 12.5 mg/dl, p<0.05) and ameliorated renal pathology (p<0.05). hKLK1-MSC transplantation significantly reduced mesangial cell (MC) proliferation, monocyte/macrophage infiltration and mesangial matrix accumulation. Using the same strategy, we treated the B6.Sle1.Sle3 mice with hKLK1-MSCs and proved that hKLK1-MSCs reduced the renal injury caused by spontaneous lupus nephritis. In conclusion, our results indicate that Kallikrein modified mesenchymal stem cell transplantation is a potent therapeutic strategy for the treatment of immune-mediated and lupus nephritis.