A 3D organoid model mimics the full spectrum of kidney branching morphogenesis!

 | Post date: 2021/07/1 | 
The mammalian kidney contains thousands of nephrons, connected to a highly branched collecting duct (CD) system. Nephrons filter and process the blood to form the primitive urine, which is collected and further refined in the CD system to adjust water, electrolytes, and pH and to maintain the homeostasis of tissue fluid. Three-dimensional (3D) multicellular mini-organ structures, or organoids, have broad applications for modeling organ development and disease, and for regenerating organs through cell or tissue replacement therapies. In a new study in Nature Communications, scientists at the Keck School of Medicine of USC were able to Generate patterned kidney organoids that recapitulate the adult kidney collecting duct system. They reported the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that could be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from human pluripotent stem cells. In chemically-defined culture conditions, UB organoids generate CD organoids, with differentiated principal and intercalated cells adopting spatial assemblies reflective of the adult kidney’s collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Applying an efficient gene editing strategy to remove RET activity, they demonstrated genetically modified UB organoids could model congenital anomalies of kidney and urinary tract.
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