A Simple Bioreactor-Based Method to Generate Kidney Organoids from Pluripotent Stem Cells

Stem Cell Reports
Aneta PrzepiorskiAlan J Davidson

Abstract

Kidney organoids made from pluripotent stem cells have the potential to revolutionize how kidney development, disease, and injury are studied. Current protocols are technically complex, suffer from poor reproducibility, and have high reagent costs that restrict scalability. To overcome some of these issues, we have established a simple, inexpensive, and robust method to grow kidney organoids in bulk from human induced pluripotent stem cells. Our organoids develop tubular structures by day 8 and show optimal tissue morphology at day 14. A comparison with fetal human kidneys suggests that day-14 organoid tissue most closely resembles late capillary loop stage nephrons. We show that deletion of HNF1B, a transcription factor linked to congenital kidney defects, interferes with tubulogenesis, validating our experimental system for studying renal developmental biology. Taken together, our protocol provides a fast, efficient, and cost-effective method for generating large quantities of human fetal kidney tissue, enabling the study of normal and aberrant kidney development.

Citations

Feb 3, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Hidekazu Naganuma, Ryuichi Nishinakamura
Mar 8, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Tomoya MiyoshiRyuji Morizane
Mar 14, 2019·Current Opinion in Nephrology and Hypertension·Pinyuan Tian, Rachel Lennon
Oct 3, 2019·Genes & Development·Melissa H Little, Alexander N Combes
May 23, 2019·Médecine sciences : M/S·Clara SteichenThierry Hauet
Apr 14, 2020·Experimental Biology and Medicine·Binbin Pan, Guoping Fan
Dec 7, 2019·Cellular and Molecular Life Sciences : CMLS·Marije KoningTon J Rabelink
Mar 22, 2020·Journal of the American Society of Nephrology : JASN·Jennifer A HollywoodTeresa M Holm
May 8, 2020·Npj Regenerative Medicine·Thomas GeuensVanessa L S LaPointe
Mar 3, 2020·Tissue Engineering and Regenerative Medicine·Marina V Pryzhkova, Philip W Jordan
Mar 10, 2020·American Journal of Physiology. Renal Physiology·Jenny L M DigbyVeronika Sander
Aug 25, 2020·Stem Cells International·Patrícia de Carvalho RibeiroHeloisa Cristina Caldas
Jun 1, 2019·Stem Cells International·Teresa P SilvaTiago G Fernandes
Aug 7, 2019·Nature Reviews. Nephrology·Ryuichi Nishinakamura
Mar 2, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Susan VeissiJitske Jansen
May 9, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Melissa H Little, Catherine Quinlan
Jan 25, 2019·Genome Medicine·Alexander N CombesMelissa H Little
Nov 30, 2019·Experimental & Molecular Medicine·Sun Ah NamYong Kyun Kim
Mar 22, 2019·Nature Materials·Susana M Chuva de Sousa Lopes
Apr 15, 2020·Annals of Biomedical Engineering·Katya D'CostaMilica Radisic
Dec 18, 2020·Developmental Biology·Melissa H Little
Dec 31, 2020·STAR Protocols·Veronika SanderAlan J Davidson
Nov 6, 2020·Developmental Biology·Nicola GrittiVikas Trivedi
Feb 6, 2021·Tissue Engineering. Part C, Methods·Charlotte J A Olde HanhofJoost G Hoenderop
Dec 1, 2020·Frontiers in Physiology·Ricardo Romero-GuevaraChristodoulos Xinaris
Jan 29, 2021·Nature Materials·Benjamin D Humphreys
Feb 2, 2021·Biomechanics and Modeling in Mechanobiology·Mohammad Amin HajariXiongbiao Chen
Jul 1, 2020·Acta Physiologica·Gijs A C FrankenJeroen H F de Baaij
Nov 18, 2020·Nature Materials·Elena GarretaNuria Montserrat
Jan 1, 2021·Cancers·Allison A FitzgeraldLouis M Weiner
Feb 18, 2021·In Vitro Cellular & Developmental Biology. Animal·Seiji KishiCraig R Brooks
Apr 19, 2020·Seminars in Nephrology·Aneta PrzepiorskiAlan J Davidson
Mar 1, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Sanchita RauthMoorthy P Ponnusamy
Feb 14, 2021·Npj Regenerative Medicine·Thomas GeuensVanessa L S LaPointe
Feb 12, 2021·Development, Growth & Differentiation·Tatsuya ShimizuKenji Osafune
Dec 24, 2020·Small·Ellen FritscheKatharina Koch
Apr 25, 2021·Acta Biomaterialia·João F Crispim, Keita Ito
May 13, 2021·Journal of Toxicology·Holly H Birdsall, Timothy G Hammond

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Methods Mentioned

BETA
size filtration
electron microscopy
mechanical dissociation
dissect
transfection
fluorescence-activated cell sorting
PCR

Software Mentioned

COSMID
RGEN
ImageJ
CCtop

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