Induced pluripotent stem cell-derived podocyte-like cells as models for assessing mechanisms underlying heritable disease phenotype: Initial studies using two alport syndrome patient lines indicate impaired potassium channel activity

Abstract

Renal podocyte survival depends upon the dynamic regulation of a complex cell architecture that links the glomerular basement membrane to integrins, ion channels, and receptors. Alport syndrome is a heritable chronic kidney disease where mutations in a3, a4, or a5 collagen genes promote podocyte death. In rodent models of renal failure, activation of the calcium-sensing receptor (CaSR) can protect podocytes from stress-related death. In this study, we assessed CaSR function in podocyte-like cells derived from induced-pluripotent stem cells from two patients with Alport Syndrome (AS1 & AS2) and a renal disease free individual [normal human mesangial cell (NHMC)], as well as a human immortaliz..