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Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

A fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at differe...

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Autores principales: Kumar Gupta, Ashwani, Sarkar, Prasenjit, Wertheim, Jason A., Pan, Xinchao, Carroll, Thomas J., Oxburgh, Leif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214420/
https://www.ncbi.nlm.nih.gov/pubmed/32393756
http://dx.doi.org/10.1038/s42003-020-0948-7
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author Kumar Gupta, Ashwani
Sarkar, Prasenjit
Wertheim, Jason A.
Pan, Xinchao
Carroll, Thomas J.
Oxburgh, Leif
author_facet Kumar Gupta, Ashwani
Sarkar, Prasenjit
Wertheim, Jason A.
Pan, Xinchao
Carroll, Thomas J.
Oxburgh, Leif
author_sort Kumar Gupta, Ashwani
collection PubMed
description A fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and heterochronic organoids were well vascularized when engrafted under the kidney capsule. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed, but despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study. We propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop similar stromal overgrowth when engrafted under the kidney capsule.
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spelling pubmed-72144202020-05-14 Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids Kumar Gupta, Ashwani Sarkar, Prasenjit Wertheim, Jason A. Pan, Xinchao Carroll, Thomas J. Oxburgh, Leif Commun Biol Article A fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and heterochronic organoids were well vascularized when engrafted under the kidney capsule. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed, but despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study. We propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop similar stromal overgrowth when engrafted under the kidney capsule. Nature Publishing Group UK 2020-05-11 /pmc/articles/PMC7214420/ /pubmed/32393756 http://dx.doi.org/10.1038/s42003-020-0948-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kumar Gupta, Ashwani
Sarkar, Prasenjit
Wertheim, Jason A.
Pan, Xinchao
Carroll, Thomas J.
Oxburgh, Leif
Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
title Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
title_full Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
title_fullStr Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
title_full_unstemmed Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
title_short Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
title_sort asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214420/
https://www.ncbi.nlm.nih.gov/pubmed/32393756
http://dx.doi.org/10.1038/s42003-020-0948-7
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