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    Vascular deficiencies in renal organoids and ex vivo kidney organogenesis

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    Name:
    DEVELOPMENTALBIOLOGY-D-20-0023 ...
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    22.35Mb
    Format:
    PDF
    Description:
    Final Accepted Manuscript
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    Author
    Ryan, Anne R
    England, Alicia R
    Chaney, Christopher P
    Cowdin, Mitzy A
    Hiltabidle, Max
    Daniel, Edward
    Gupta, Ashwani Kumar
    Oxburgh, Leif
    Carroll, Thomas J
    Cleaver, Ondine
    Affiliation
    University of Arizona
    Issue Date
    2021-05-15
    Keywords
    Angioblast
    Blood vessel
    Cord
    Endothelial cell
    Kidney
    Organoid
    RNAseq
    
    Metadata
    Show full item record
    Publisher
    Elsevier Inc.
    Citation
    Ryan, 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.
    Journal
    Developmental Biology
    Rights
    Copyright © 2021. Published by Elsevier Inc.
    Collection Information
    This 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 repository@u.library.arizona.edu.
    Abstract
    Chronic 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.
    Note
    12 month embargo; available online 15 May 2021
    EISSN
    1095-564X
    PubMed ID
    34000274
    DOI
    10.1016/j.ydbio.2021.04.009
    Version
    Final accepted manuscript
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ydbio.2021.04.009
    Scopus Count
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    UA Faculty Publications

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