Effective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies

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dc.contributor.authorHyun Mi Kang-
dc.contributor.authorJung Hwa Lim-
dc.contributor.authorKyung Hee Noh-
dc.contributor.authorDongmin Park-
dc.contributor.authorHyun Soo Cho-
dc.contributor.authorK Susztak-
dc.contributor.authorCho Rok Jung-
dc.date.accessioned2020-02-07T16:30:39Z-
dc.date.available2020-02-07T16:30:39Z-
dc.date.issued2019-
dc.identifier.issn2045-2322-
dc.identifier.uri10.1038/s41598-019-53855-2ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/19171-
dc.description.abstractStable and reproducible kidney cellular models could accelerate our understanding of diseases, help therapeutics development, and improve nephrotoxicity screenings. Generation of a reproducible in vitro kidney models has been challenging owing to the cellular heterogeneity and structural complexity of the kidney. We generated mixed immortalized cell lines that stably maintained their characteristic expression of renal epithelial progenitor markers for the different lineages of kidney cellular compartments via the BMP7 signaling pathway from a mouse and a human whole kidney. These cells were used to generate functional and matured kidney spheroids containing multiple renal lineages, such as the proximal tubule, loop of Henle, distal tubules, and podocytes, using extracellular matrix and physiological force, named spheroid-forming unit (SFU). They expressed all apical and basolateral transporters that are important for drug metabolism and displayed key functional aspects of the proximal tubule, including protein endocytosis and increased gamma-glutamyltransferase activity, and cyclic AMP responded to external cues, such as parathyroid hormone. Following exposure, cells fluxed and took up drugs via proximal tubule-specific apical or basolateral transporters, and displayed increased cell death and expression of renal injury marker. Here, we developed a new differentiation method to generate kidney spheroids that structurally recapitulate important features of the kidney effectively and reproducibly using mixed immortalized renal cells, and showed their application for renal toxicity studies.-
dc.publisherSpringer-Nature Pub Group-
dc.titleEffective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies-
dc.title.alternativeEffective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies-
dc.typeArticle-
dc.citation.titleScientific Reports-
dc.citation.number0-
dc.citation.endPage17610-
dc.citation.startPage17610-
dc.citation.volume9-
dc.contributor.affiliatedAuthorHyun Mi Kang-
dc.contributor.affiliatedAuthorJung Hwa Lim-
dc.contributor.affiliatedAuthorKyung Hee Noh-
dc.contributor.affiliatedAuthorDongmin Park-
dc.contributor.affiliatedAuthorHyun Soo Cho-
dc.contributor.affiliatedAuthorCho Rok Jung-
dc.contributor.alternativeName강현미-
dc.contributor.alternativeName임정화-
dc.contributor.alternativeName노경희-
dc.contributor.alternativeName박동민-
dc.contributor.alternativeName조현수-
dc.contributor.alternativeNameSusztak-
dc.contributor.alternativeName정초록-
dc.identifier.bibliographicCitationScientific Reports, vol. 9, pp. 17610-17610-
dc.identifier.doi10.1038/s41598-019-53855-2-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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