Application of genetically engineered tubular epithelial cells in kidney disease.
We constructed an ex vivo gene transfer system to deliver cytokines into the kidney and circulation using genetically modified renal tubular epithelial cells (TEC). TEC were infected with recombinant retroviruses expressing macrophage (Mphi) growth factors using a retroviral Moloney murine leukemia virus-based MFG vector. These infected TEC have the capacity to secrete stable and sustained amounts of cytokines for prolonged periods (>4 months) in vitro and in vivo (>28 days). Implanting genetically modified TEC secreting Mphi growth factors under the kidney capsule initiates severe local renal injury in mice with a deficiency in Fas (Faslpr gene). This system offers a novel and powerful approach to probe for the impact of sustained cytokine expression in the progression of kidney destruction.
Yokoyama
H
H
Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, USA.
Naito
T
T
Wada
T
T
Kelley
V R
VR
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008979:Moloney murine leukemia virus / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor