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Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture
During early developmental stages, embryonic kidneys are not fully vascularized and are potentially exposed to hypoxic conditions, which is known to influence cell proliferation and survival, ureteric bud branching, and vascularization of the developing kidney. To optimize the culture conditions of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774677/ https://www.ncbi.nlm.nih.gov/pubmed/36551007 http://dx.doi.org/10.3390/bioengineering9120801 |
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author | Hamon, Morgan Cheng, Hsiao-Min Johnson, Ming Yanagawa, Norimoto Hauser, Peter V. |
author_facet | Hamon, Morgan Cheng, Hsiao-Min Johnson, Ming Yanagawa, Norimoto Hauser, Peter V. |
author_sort | Hamon, Morgan |
collection | PubMed |
description | During early developmental stages, embryonic kidneys are not fully vascularized and are potentially exposed to hypoxic conditions, which is known to influence cell proliferation and survival, ureteric bud branching, and vascularization of the developing kidney. To optimize the culture conditions of in vitro cultured kidneys and gain further insight into the effect of hypoxia on kidney development, we exposed mouse embryonic kidneys isolated at E11.5, E12.5, and E13.5 to hypoxic and normal culture conditions and compared ureteric bud branching patterns, the growth of the progenitor subpopulation hoxb7+, and the expression patterns of progenitor and differentiation markers. Branching patterns were quantified using whole organ confocal imaging and gradient-vector-based analysis. In our model, hypoxia causes an earlier expression of UB tip cell markers, and a delay in stalk cell marker gene expression. The metanephric mesenchyme (MM) exhibited a later expression of differentiation marker FGF8, marking a delay in nephron formation. Hypoxia further delayed the expression of stroma cell progenitor markers, a delay in cortical differentiation markers, as well as an earlier expression of medullary and ureteral differentiation markers. We conclude that standard conditions do not apply universally and that tissue engineering strategies need to optimize suitable culture conditions for each application. We also conclude that adapting culture conditions to specific aspects of organ development in tissue engineering can help to improve individual stages of tissue generation. |
format | Online Article Text |
id | pubmed-9774677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97746772022-12-23 Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture Hamon, Morgan Cheng, Hsiao-Min Johnson, Ming Yanagawa, Norimoto Hauser, Peter V. Bioengineering (Basel) Article During early developmental stages, embryonic kidneys are not fully vascularized and are potentially exposed to hypoxic conditions, which is known to influence cell proliferation and survival, ureteric bud branching, and vascularization of the developing kidney. To optimize the culture conditions of in vitro cultured kidneys and gain further insight into the effect of hypoxia on kidney development, we exposed mouse embryonic kidneys isolated at E11.5, E12.5, and E13.5 to hypoxic and normal culture conditions and compared ureteric bud branching patterns, the growth of the progenitor subpopulation hoxb7+, and the expression patterns of progenitor and differentiation markers. Branching patterns were quantified using whole organ confocal imaging and gradient-vector-based analysis. In our model, hypoxia causes an earlier expression of UB tip cell markers, and a delay in stalk cell marker gene expression. The metanephric mesenchyme (MM) exhibited a later expression of differentiation marker FGF8, marking a delay in nephron formation. Hypoxia further delayed the expression of stroma cell progenitor markers, a delay in cortical differentiation markers, as well as an earlier expression of medullary and ureteral differentiation markers. We conclude that standard conditions do not apply universally and that tissue engineering strategies need to optimize suitable culture conditions for each application. We also conclude that adapting culture conditions to specific aspects of organ development in tissue engineering can help to improve individual stages of tissue generation. MDPI 2022-12-14 /pmc/articles/PMC9774677/ /pubmed/36551007 http://dx.doi.org/10.3390/bioengineering9120801 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hamon, Morgan Cheng, Hsiao-Min Johnson, Ming Yanagawa, Norimoto Hauser, Peter V. Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture |
title | Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture |
title_full | Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture |
title_fullStr | Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture |
title_full_unstemmed | Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture |
title_short | Effect of Hypoxia on Branching Characteristics and Cell Subpopulations during Kidney Organ Culture |
title_sort | effect of hypoxia on branching characteristics and cell subpopulations during kidney organ culture |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774677/ https://www.ncbi.nlm.nih.gov/pubmed/36551007 http://dx.doi.org/10.3390/bioengineering9120801 |
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