Intravenous Renal Cell Transplantation for Polycystic Kidney Disease.

摘要

Polycystic kidney disease (PKD), the most common life threatening genetic disease and affects approximately 1:400 people in the US including significant numbers of Active Duty Military personnel, Veterans and their beneficiaries. In PKD, the affected renal epithelia form cysts, eventually destroying renal architecture and function, leading to chronic kidney disease and end stage renal disease. There is currently no specific therapy for PKD. The present research examines the innovative translational therapy of intravenous administration of adult renal tubule cells containing the wild type (normal) PKD Pkhd1 gene in experimental PKD (the PCK rat model). The aim is to replace abnormal renal epithelia while avoiding the morbidity and mortality of surgery. Expansion of cells in vitro will also extend the utility of organs available for transplant. Data obtained to date demonstrate markedly lower renal cyst volume and fibrosis and better kidney function with cell transplantation. There are two potential mechanisms of action, either transfer of genetic material via exo-RNA or re-orientation of the cystogenic phenotype by correction of abnormalities in planar polarity. These results are the basis for an additional funding pre-application to extend the present studies, ultimately to prevent or treat kidney failure in humans. The results will also be presented at the Annual Meeting of the American Society of Nephrology in November, 2013.