Vascular deficiencies in renal organoids and ex vivo kidney organogenesis
AuthorRyan, Anne R
England, Alicia R
Chaney, Christopher P
Cowdin, Mitzy A
Gupta, Ashwani Kumar
Carroll, Thomas J
AffiliationUniversity of Arizona
MetadataShow full item record
CitationRyan, A. R., England, A. R., Chaney, C. P., Cowdin, M. A., Hiltabidle, M., Daniel, E., Gupta, A. K., Oxburgh, L., Carroll, T. J., & Cleaver, O. (2021). Vascular deficiencies in renal organoids and ex vivo kidney organogenesis. Developmental Biology, 477, 98–116.
RightsCopyright © 2021. Published by Elsevier Inc.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractChronic kidney disease (CKD) and end stage renal disease (ESRD) are increasingly frequent and devastating conditions that have driven a surge in the need for kidney transplantation. A stark shortage of organs has fueled interest in generating viable replacement tissues ex vivo for transplantation. One promising approach has been self-organizing organoids, which mimic developmental processes and yield multicellular, organ-specific tissues. However, a recognized roadblock to this approach is that many organoid cell types fail to acquire full maturity and function. Here, we comprehensively assess the vasculature in two distinct kidney organoid models as well as in explanted embryonic kidneys. Using a variety of methods, we show that while organoids can develop a wide range of kidney cell types, as previously shown, endothelial cells (ECs) initially arise but then rapidly regress over time in culture. Vasculature of cultured embryonic kidneys exhibit similar regression. By contrast, engraftment of kidney organoids under the kidney capsule results in the formation of a stable, perfused vasculature that integrates into the organoid. This work demonstrates that kidney organoids offer a promising model system to define the complexities of vascular-nephron interactions, but the establishment and maintenance of a vascular network present unique challenges when grown ex vivo.
Note12 month embargo; available online 15 May 2021
VersionFinal accepted manuscript
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