Engineered Stem Cell Models to Reconstitute Kidney Function and Disease

Glomerulopathy is a leading cause of end-stage renal failure. An in vitro model of human glomerulus could facilitate therapeutic discovery and illuminate kidney disease mechanisms. Efforts to develop such models are limited by the lack of functional human podocytes, the specialized epithelial cells that encase glomerular capillaries and regulate selective permeability in the glomerulus. We developed a highly efficient method for directed differentiation of human induced pluripotent stem (iPS) cells into mature podocytes. By using microfluidic organs-on-chips devices, we engineered an in vitro model of the human glomerular capillary wall that supports podocyte differentiation and recapitulate the normal tissue-tissue interface (podocytes―basement membrane―endothelium) and selective molecular filtration of the glomerulus. The engineered human glomerulus-on-a-chip also replicates kidney disease phenotypes in vitro. Our results demonstrate the feasibility of generating mature podocytes in a robust manner, providing an opportunity to engineer a functional human glomerular capillary wall-on-a-chip. This work could illuminate the mechanisms of human kidney disease, and provide a functional in vitro system for therapeutic development. These results also provide opportunities for personalized medicine, cell therapy, and regenerative medicine.