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      Targeting Genetically Modified Macrophages to the Glomerulus


      Cardiorenal Medicine

      S. Karger AG

      Inflammation, Glomerulonephritis, Adenovirus, Gene, Macrophages

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          Macrophages are key players in the development of the majority of renal diseases and are therefore ideal cellular vectors for site specifically targeting gene therapy to inflamed glomeruli. Macrophages can be genetically modified using viral vectors ex vivo then re-introduced into the body where they can home to the diseased site. This review summarises current experience in efficiently targeting modified macrophages to the inflamed glomerulus focussing on the factors controlling macrophage localisation, macrophage gene transfer methods, in vivo gene delivery and results of recent investigations using modified macrophage gene therapy for glomerular disease.

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          Most cited references 4

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          Is Open Access

          Bone-marrow-derived macrophages genetically modified to produce IL-10 reduce injury in experimental glomerulonephritis.

          Macrophages are intimately involved in the development of immune-mediated inflammation, including glomerulonephritis. We have transduced primary cultures of macrophages to express IL-10 and tested the ability of these cells to control rat nephrotoxic nephritis (NTN), a model of human glomerulonephritis. Ad-IL-10-transduced bone-marrow-derived macrophages (BMDM) produced large amounts of IL-10 in culture, and their TNF-alpha production was decreased in response to interferon-gamma and LPS. Transduced macrophages were injected into the renal artery of rats, 6 h after the induction of NTN, where they localized efficiently to inflamed rat glomeruli. Delivery of IL-10-expressing macrophages to nephritic rats produced a marked reduction in albuminuria compared with unmodified NTN or injection of Ad-null-transduced BMDM. IL-10 treatment decreased the number of glomerular ED1- and ED3-positive cells, MHC class II expression, and the number of fibrinoid lesions. Interestingly, anti-inflammatory changes in the Ad-IL-10-injected kidney were mirrored by changes in the contralateral kidney. These results highlight that Ad-IL-10-transduced macrophages infiltrate inflamed glomeruli and reduce the severity of glomerular inflammation, emphasizing the value of local delivery of genetically modified macrophages in the manipulation of inflammatory disease.
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            Genetically modified bone marrow continuously supplies anti-inflammatory cells and suppresses renal injury in mouse Goodpasture syndrome

             T Yokoo (2001)
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              Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus


                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                August 2003
                17 November 2004
                : 94
                : 4
                : e113-e118
                Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland
                72494 Nephron Exp Nephrol 2003;94:e113–e118
                © 2003 S. Karger AG, Basel

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                Page count
                Figures: 1, References: 20, Pages: 1
                Self URI (application/pdf):

                Cardiovascular Medicine, Nephrology

                Macrophages, Gene, Adenovirus, Glomerulonephritis, Inflammation


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