Gene therapy for glomerulonephritis using bone marrow stem cells

Abstract

We have proposed two novel therapeutic strategies for glomerulonephritis based on bone marrow transplantation technology. In the ex vivo differentiation system, bone marrow cells were differentiated ex vivo to express ligands of adhesion molecules and acquire the potential to be recruited to the inflamed site, and they were adenovirally transfected with a therapeutic gene followed by transfusion to affected subjects. These cells may deliver anti-inflammatory cytokines into inflamed glomeruli. In the in vivo differentiation system, bone marrow cells were genetically modified using a retrovirus and transplanted to the affected subjects before differentiation so that they might retain the potential for self-renewal as well as differentiation in vivo. Both systems were able to prove the therapeutic benefit in at least anti-glomerular basement membrane (anti-GBM) nephritis in mice. These strategies have several advantages over the previous glomerulus-targeted gene-delivery system, i.e., use of peripheral vessels for administration, and possibly no immunoreaction due to autologous transfer, and suggest that bone marrow-derived cells can be utilized for therapeutic intervention to treat glomerulonephritis.