Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule
Abstract Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining the functions of the proximal tubule epithelial layer—selective filtration and reabsorption. In this report, pseudo proximal tubule cells extracted f...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04862-7 |
| _version_ | 1797831944302493696 |
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| author | Ramin Banan Sadeghian Ryohei Ueno Yuji Takata Akihiko Kawakami Cheng Ma Toshikazu Araoka Minoru Takasato Ryuji Yokokawa |
| author_facet | Ramin Banan Sadeghian Ryohei Ueno Yuji Takata Akihiko Kawakami Cheng Ma Toshikazu Araoka Minoru Takasato Ryuji Yokokawa |
| author_sort | Ramin Banan Sadeghian |
| collection | DOAJ |
| description | Abstract Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining the functions of the proximal tubule epithelial layer—selective filtration and reabsorption. In this report, pseudo proximal tubule cells extracted from human-induced pluripotent stem cell-derived kidney organoids are combined and cultured with immortalized proximal tubule cells. It is shown that the cocultured tissue is an impervious epithelium that offers improved levels of certain transporters, extracellular matrix proteins collagen and laminin, and superior glucose transport and P-glycoprotein activity. mRNA expression levels higher than those obtained from each cell type were detected, suggesting an anomalous synergistic crosstalk between the two. Alongside, the improvements in morphological characteristics and performance of the immortalized proximal tubule tissue layer exposed, upon maturation, to human umbilical vein endothelial cells are thoroughly quantified and compared. Glucose and albumin reabsorption, as well as xenobiotic efflux rates through P-glycoprotein were all improved. The data presented abreast highlight the advantages of the cocultured epithelial layer and the non-iPSC-based bilayer. The in vitro models presented herein can be helpful in personalized nephrotoxicity studies. |
| first_indexed | 2024-04-09T13:59:47Z |
| format | Article |
| id | doaj.art-3ca6e124d72a4236b880fb504ef58367 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-09T13:59:47Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-3ca6e124d72a4236b880fb504ef583672023-05-07T11:20:56ZengNature PortfolioCommunications Biology2399-36422023-05-016111710.1038/s42003-023-04862-7Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubuleRamin Banan Sadeghian0Ryohei Ueno1Yuji Takata2Akihiko Kawakami3Cheng Ma4Toshikazu Araoka5Minoru Takasato6Ryuji Yokokawa7Department of Micro Engineering, Kyoto UniversityDepartment of Micro Engineering, Kyoto UniversityDepartment of Micro Engineering, Kyoto UniversityDepartment of Micro Engineering, Kyoto UniversityDepartment of Micro Engineering, Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityRIKEN Center for Biosystems Dynamics Research (BDR)Department of Micro Engineering, Kyoto UniversityAbstract Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining the functions of the proximal tubule epithelial layer—selective filtration and reabsorption. In this report, pseudo proximal tubule cells extracted from human-induced pluripotent stem cell-derived kidney organoids are combined and cultured with immortalized proximal tubule cells. It is shown that the cocultured tissue is an impervious epithelium that offers improved levels of certain transporters, extracellular matrix proteins collagen and laminin, and superior glucose transport and P-glycoprotein activity. mRNA expression levels higher than those obtained from each cell type were detected, suggesting an anomalous synergistic crosstalk between the two. Alongside, the improvements in morphological characteristics and performance of the immortalized proximal tubule tissue layer exposed, upon maturation, to human umbilical vein endothelial cells are thoroughly quantified and compared. Glucose and albumin reabsorption, as well as xenobiotic efflux rates through P-glycoprotein were all improved. The data presented abreast highlight the advantages of the cocultured epithelial layer and the non-iPSC-based bilayer. The in vitro models presented herein can be helpful in personalized nephrotoxicity studies.https://doi.org/10.1038/s42003-023-04862-7 |
| spellingShingle | Ramin Banan Sadeghian Ryohei Ueno Yuji Takata Akihiko Kawakami Cheng Ma Toshikazu Araoka Minoru Takasato Ryuji Yokokawa Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule Communications Biology |
| title | Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule |
| title_full | Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule |
| title_fullStr | Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule |
| title_full_unstemmed | Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule |
| title_short | Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule |
| title_sort | cells sorted off hipsc derived kidney organoids coupled with immortalized cells reliably model the proximal tubule |
| url | https://doi.org/10.1038/s42003-023-04862-7 |
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