Modelling Hereditary Kidney Disease using Induced Pluripotent Stem Cells and Organoids

The epidemic of chronic kidney disease (CKD) and end-stage renal failure represents a crisis for health world-wide. Recent work indicates that CKD may have a genetic basis, and genome-wide studies suggest that genetic background substantially influences an individual’s lifetime risk for kidney disease. Inherited renal disease accounts for ESRF incidence in 50% of children and 20% of adults with the disease. Alport syndrome is one of these genetic kidney diseases; it affects one in 10,000 individuals and invariably leads to end-stage renal failure. The landmark discovery of reprogramming adult cells to generate induced pluripotent stem cells (iPSC) opened an unprecedented opportunity to elucidate disease mechanisms in vitro, to carry out drug-screening and toxicology studies, and to advance cell-replacement therapy in regenerative medicine. We have generated a bank of iPSCs from patients with inherited kidney disease including Alport syndrome, Fabry disease and polycystic kidney disease. These cell lines will be a valuable tool for understanding how mutations cause disease, for screening new drugs, to develop disease-modifying assays, and to test for autologous cell-replacement therapies. These cell lines can provide information that enables clinicians to optimize personalised medical care for affected individuals, and opens up new avenues for therapeutically targeted remediation. In the long-term, the autologous transplantation of patient-derived kidney iPS cells with correction of the underlying genetic defect represents an innovative approach for kidney cellular replacement. will be a valuable tool for understanding how particular mutation/s cause disease, for screening new drugs, to develop disease-modifying assays, and to test for autologous cell-replacement therapies.