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filingDate 2016-09-16-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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publicationDate 2018-09-13-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber US-2018258404-A1
titleOfInvention Methods of generating nephrons from human pluripotent stem cells
abstract The Inventors established an efficient, chemically defined protocol for differentiating hPSCs into multi-potent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, the Inventors generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-pattern into nephron structures. In both 2D and 3D culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle, and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. The Inventors also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.
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