Musah, SamiraMammoto, AkikoFerrante, ThomasJeanty, SauveurHirano-Kobayashi, MarikoMammoto, TadanoriRoberts, KristenChung, SeyoonNovak, RichardIngram, MilesFatanat-Didar, TohidKoshy, SandeepWeaver, JamesChurch, GeorgeIngber, Donald2017-12-062017Musah, S., A. Mammoto, T. C. Ferrante, S. S. F. Jeanty, M. Hirano-Kobayashi, T. Mammoto, K. Roberts, et al. 2017. “Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.” Nature biomedical engineering 1 (1): 0069. doi:10.1038/s41551-017-0069. http://dx.doi.org/10.1038/s41551-017-0069.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493305An in vitro model of the human kidney glomerulus — the major site of blood filtration — could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes — the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2−) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications.en-USJournal Article2017-12-0610.1038/s41551-017-0069