Flow-enhanced vascularization and maturation of kidney organoids in vitro
Open accessAbstract
Kidney organoids derived from human pluripotent stem cells have glomerular- and tubular-like compartments that are largely avascular and immature in static culture. Here we report an in vitro method for culturing kidney organoids under flow on millifluidic chips, which expands their endogenous pool of endothelial progenitor cells and generates vascular networks with perfusable lumens surrounded by mural cells. We found that vascularized kidney organoids cultured under flow had more mature podocyte and tubular compartments with enhanced cellular polarity and adult gene expression compared with that in static controls. Glomerular vascular development progressed through intermediate stages akin to those involved in the embryonic mammalian kidney's formation of capillary loops abutting foot processes. The association of vessels with these compartments was reduced after disruption of the endogenous VEGF gradient. The ability to induce substantial vascularization and morphological maturation of kidney organoids in vitro under flow opens new avenues for studies of kidney development, disease, and regeneration.
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OoC devices have improved the characteristics of hPSC-derived pancreatic islets, intestinal, stomach, and liver organoids by supporting physiological flow rates.
“OoC devices have improved the characteristics of hPSC-derived pancreatic islets104, intestinal105, stomach106, and liver77 organoids by supporting physiological flow rates.”
From Organoids (2022) · cites this paper as [106]
Citation 77 is attached to liver organoids, but the cited paper studies hPSC-derived kidney organoids. The Results section, “Developing kidney organoids exhibit enhanced vascularization under flow” (page unavailable), reports improved vascularization of kidney organoids under flow, not liver organoids. (LLM, conf=0.88)
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- Authors
- Homan, K. A., Gupta, N., Kroll, K. T., Kolesky, D. B., Skylar-Scott, M., Miyoshi, T., Mau, D., Valerius, M. T., Ferrante, T., Bonventre, J. V., Lewis, J. A., & Morizane, R.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Lewis, Jennifer A.
- Morizane, Ryuji
- ORCID
- Venue
- Nature Methods
- Published
- 2019-02-11
- Volume
- 16
- Issue
- 3
- Pages
- 255-262
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC6488032
- OpenAlex
- W2913348902
- Cited by
- 939
- References
- 31
- Citations by year
- 2026: 135 · 2025: 120 · 2024: 156 · 2023: 125 · 2022: 147 · 2021: 122 · 2020: 85 · 2019: 48
- FWCI
- 33.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UH3TR002155, UG3TR002155)
- McDonnell Center for Systems Neuroscience
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK039773, P30DK079333, U01DK107350, T32DK007527, U24DK076169, R01DK072381, R01DK039773)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- kidney organoids, vascularization, endothelial progenitor cells, glomerular development, podocytes, pluripotent stem cells, kidney development, organoid maturation
- MeSH terms
- Cells, Cultured, Fibroblasts, Humans, Kidney, Organ Culture Techniques, Organoids, Tissue Engineering, Lab-On-A-Chip Devices, Human Umbilical Vein Endothelial Cells, In Vitro Techniques, Printing, Three-Dimensional
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