Cell-specific targeting of renal fibrosis

Focus of this thesis is to demonstrate the benefit of cell specific targeted delivery to attenuate graft rejection, inflammation and fibrosis in the animal models of kidney disease. We provide a novel strategy of drug delivery to proximal tubular cells by using megalin receptor, and to myofibroblasts by directing anti-fibrotic cytokine to PDGFR. These strategies increase drug therapeutic potential due to enhanced efficacy and reduced off-target side effects. We believe cell-specific drug delivery is a promising approach to effectively halt renal fibrosis. Moreover, the ex vivo model which we described here is a novel tool to test the pathophysiology of early onset as well as end-stage of fibrosis and to screen the efficacy of anti-fibrotic drugs ex vivo in a multicellular and pro-fibrotic milieu. Major advantage of the slice model is that the data from our animal study can be directly extrapolated to human situation by using (fibrotic) human kidney tissue. Importantly, tissue slices is an alternative or 3R methods which give insight into mechanisms of disease processes and is designed to replace, reduce, and refine animal experiments.