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Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics

Acute kidney injury (AKI) is an increasingly common problem afflicting all ages, occurring in over 20% of non-critically ill hospitalized patients and >30% of children and >50% of adults in critical care units. AKI is associated with serious short-term and long-term consequences, and current t...

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Autores principales: Pode-Shakked, Naomi, Devarajan, Prasad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266524/
https://www.ncbi.nlm.nih.gov/pubmed/35806216
http://dx.doi.org/10.3390/ijms23137211
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author Pode-Shakked, Naomi
Devarajan, Prasad
author_facet Pode-Shakked, Naomi
Devarajan, Prasad
author_sort Pode-Shakked, Naomi
collection PubMed
description Acute kidney injury (AKI) is an increasingly common problem afflicting all ages, occurring in over 20% of non-critically ill hospitalized patients and >30% of children and >50% of adults in critical care units. AKI is associated with serious short-term and long-term consequences, and current therapeutic options are unsatisfactory. Large gaps remain in our understanding of human AKI pathobiology, which have hindered the discovery of novel diagnostics and therapeutics. Although animal models of AKI have been extensively studied, these differ significantly from human AKI in terms of molecular and cellular responses. In addition, animal models suffer from interspecies differences, high costs and ethical considerations. Static two-dimensional cell culture models of AKI also have limited utility since they have focused almost exclusively on hypoxic or cytotoxic injury to proximal tubules alone. An optimal AKI model would encompass several of the diverse specific cell types in the kidney that could be targets of injury. Second, it would resemble the human physiological milieu as closely as possible. Third, it would yield sensitive and measurable readouts that are directly applicable to the human condition. In this regard, the past two decades have seen a dramatic shift towards newer personalized human-based models to study human AKI. In this review, we provide recent developments using human stem cells, organoids, and in silico approaches to advance personalized AKI diagnostics and therapeutics.
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spelling pubmed-92665242022-07-09 Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics Pode-Shakked, Naomi Devarajan, Prasad Int J Mol Sci Review Acute kidney injury (AKI) is an increasingly common problem afflicting all ages, occurring in over 20% of non-critically ill hospitalized patients and >30% of children and >50% of adults in critical care units. AKI is associated with serious short-term and long-term consequences, and current therapeutic options are unsatisfactory. Large gaps remain in our understanding of human AKI pathobiology, which have hindered the discovery of novel diagnostics and therapeutics. Although animal models of AKI have been extensively studied, these differ significantly from human AKI in terms of molecular and cellular responses. In addition, animal models suffer from interspecies differences, high costs and ethical considerations. Static two-dimensional cell culture models of AKI also have limited utility since they have focused almost exclusively on hypoxic or cytotoxic injury to proximal tubules alone. An optimal AKI model would encompass several of the diverse specific cell types in the kidney that could be targets of injury. Second, it would resemble the human physiological milieu as closely as possible. Third, it would yield sensitive and measurable readouts that are directly applicable to the human condition. In this regard, the past two decades have seen a dramatic shift towards newer personalized human-based models to study human AKI. In this review, we provide recent developments using human stem cells, organoids, and in silico approaches to advance personalized AKI diagnostics and therapeutics. MDPI 2022-06-29 /pmc/articles/PMC9266524/ /pubmed/35806216 http://dx.doi.org/10.3390/ijms23137211 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 Review
Pode-Shakked, Naomi
Devarajan, Prasad
Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
title Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
title_full Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
title_fullStr Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
title_full_unstemmed Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
title_short Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
title_sort human stem cell and organoid models to advance acute kidney injury diagnostics and therapeutics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266524/
https://www.ncbi.nlm.nih.gov/pubmed/35806216
http://dx.doi.org/10.3390/ijms23137211
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