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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Main Authors: Naomi Pode-Shakked, Prasad Devarajan
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/13/7211
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author Naomi Pode-Shakked
Prasad Devarajan
author_facet Naomi Pode-Shakked
Prasad Devarajan
author_sort Naomi Pode-Shakked
collection DOAJ
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 doaj.art-acca41ac526b4446bd5e62f80425ed852023-11-23T20:09:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313721110.3390/ijms23137211Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and TherapeuticsNaomi Pode-Shakked0Prasad Devarajan1Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, IsraelDivision of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USAAcute 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.https://www.mdpi.com/1422-0067/23/13/7211acute kidney injurykidney organoidskidney developmenttubuloids
spellingShingle Naomi Pode-Shakked
Prasad Devarajan
Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
International Journal of Molecular Sciences
acute kidney injury
kidney organoids
kidney development
tubuloids
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 acute kidney injury
kidney organoids
kidney development
tubuloids
url https://www.mdpi.com/1422-0067/23/13/7211
work_keys_str_mv AT naomipodeshakked humanstemcellandorganoidmodelstoadvanceacutekidneyinjurydiagnosticsandtherapeutics
AT prasaddevarajan humanstemcellandorganoidmodelstoadvanceacutekidneyinjurydiagnosticsandtherapeutics