Application of genetically engineered tubular epithelial cells in kidney disease

We constructed an ex vivo gene transfer system to deliver cytokines into th e kidney and circulation using genetically modified renal tubular epithelia l cells (TEC). TEC were infected with recombinant retroviruses expressing m acrophage (M phi) growth factors using a retroviral Moloney murine leukemia virus-based MFG vector. These infected TEC have the capacity to secrete st able and sustained amounts of cytokines for prolonged periods (>4 months) i n vitro and in vivo (>28 days), Implanting genetically modified TEC secreti ng M phi growth factors under the kidney capsule initiates severe local ren al injury in mice with a deficiency in Fas (Fas(lpr) gene). This system off ers a novel and powerful approach to probe for the impact of sustained cyto kine expression in the progression of kidney destruction.