Modeling Kidney Disease with iPS Cells

Biomark Insights. 2015 Dec 22;10(Suppl 1):153-69. doi: 10.4137/BMI.S20054. eCollection 2015.

Abstract

Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and 'disease in a dish' laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field.

Keywords: ADPKD; ARPKD; Alport syndrome; CRISPR; ESC; KIM-1; Wolfram syndrome; cell therapy; cilia; diabetes insipidus; diabetes mellitus; focal segmental glomerulosclerosis; genome editing; in vitro clinical trials; lupus nephritis; macular degeneration; organ replacement; podocalyxin; podocyte; proximal tubule; regeneration; transcriptome.

Publication types

  • Review