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Stem Cell Reports. 2018 Aug 14;11(2):470-484. doi: 10.1016/j.stemcr.2018.06.018. Epub 2018 Jul 19.

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

Author information

1
Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New Zealand.
2
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
3
Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia.
4
Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New Zealand. Electronic address: a.davidson@auckland.ac.nz.

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.

KEYWORDS:

3D culture; CRISPR/Cas9; HNF1B; bioreactor; embryoid body; fetal human kidney; fibrosis; iPSC; kidney organoid; renal development

PMID:
30033089
PMCID:
PMC6092837
DOI:
10.1016/j.stemcr.2018.06.018
[Indexed for MEDLINE]
Free PMC Article

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