Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine

<b>Background/Objectives</b>: Human pluripotent stem cells (hPSCs) and organoid technologies are transforming pharmaceutical research by providing models that more accurately reflect human physiology, genetic variability, and disease mechanisms. This review aims to assess how these syste...

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Main Authors: Eleanor Luce, Jean-Charles Duclos-Vallee
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/7/992
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author Eleanor Luce
Jean-Charles Duclos-Vallee
author_facet Eleanor Luce
Jean-Charles Duclos-Vallee
author_sort Eleanor Luce
collection DOAJ
description <b>Background/Objectives</b>: Human pluripotent stem cells (hPSCs) and organoid technologies are transforming pharmaceutical research by providing models that more accurately reflect human physiology, genetic variability, and disease mechanisms. This review aims to assess how these systems improve the predictive power of preclinical drug development while addressing ethical concerns and supporting the advancement of precision medicine. <b>Methods</b>: We conducted a comprehensive review of the recent literature focusing on the biological principles, technological developments, and pharmaceutical applications of hPSC- and organoid-based systems. Particular attention was given to patient-derived models, integration of omics approaches, bioengineering advances, and artificial intelligence applications in drug screening workflows. <b>Results</b>: hPSC- and organoid-based platforms outperform traditional 2D cultures and animal models in replicating human-specific pathophysiology, enabling personalized drug testing and improving predictions of therapeutic efficacy and safety. These technologies also align with the ethical principles of the 3Rs (replacement, reduction, and refinement) by reducing reliance on animal experimentation. However, challenges persist, including standardization of protocols, batch-to-batch variability, and scalability. Promising solutions involve automation, high-throughput screening, and multi-omics integration, which collectively enhance reproducibility and translational relevance. <b>Conclusions</b>: Stem cell- and organoid-based systems offer a more human-relevant, ethical, and individualized approach to biomedical research. Despite current limitations, ongoing interdisciplinary innovations are expected to accelerate their clinical and industrial adoption. Collaborative efforts will be essential to standardize methodologies and fully realize the potential of these models in bridging preclinical and clinical drug development.
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spelling doaj-art-af1f0a7221ae4eeebf1401d6018077ef2025-08-20T03:07:58ZengMDPI AGPharmaceuticals1424-82472025-07-0118799210.3390/ph18070992Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized MedicineEleanor Luce0Jean-Charles Duclos-Vallee1Unité Mixte de Recherche (UMR_S) 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, FranceUnité Mixte de Recherche (UMR_S) 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, France<b>Background/Objectives</b>: Human pluripotent stem cells (hPSCs) and organoid technologies are transforming pharmaceutical research by providing models that more accurately reflect human physiology, genetic variability, and disease mechanisms. This review aims to assess how these systems improve the predictive power of preclinical drug development while addressing ethical concerns and supporting the advancement of precision medicine. <b>Methods</b>: We conducted a comprehensive review of the recent literature focusing on the biological principles, technological developments, and pharmaceutical applications of hPSC- and organoid-based systems. Particular attention was given to patient-derived models, integration of omics approaches, bioengineering advances, and artificial intelligence applications in drug screening workflows. <b>Results</b>: hPSC- and organoid-based platforms outperform traditional 2D cultures and animal models in replicating human-specific pathophysiology, enabling personalized drug testing and improving predictions of therapeutic efficacy and safety. These technologies also align with the ethical principles of the 3Rs (replacement, reduction, and refinement) by reducing reliance on animal experimentation. However, challenges persist, including standardization of protocols, batch-to-batch variability, and scalability. Promising solutions involve automation, high-throughput screening, and multi-omics integration, which collectively enhance reproducibility and translational relevance. <b>Conclusions</b>: Stem cell- and organoid-based systems offer a more human-relevant, ethical, and individualized approach to biomedical research. Despite current limitations, ongoing interdisciplinary innovations are expected to accelerate their clinical and industrial adoption. Collaborative efforts will be essential to standardize methodologies and fully realize the potential of these models in bridging preclinical and clinical drug development.https://www.mdpi.com/1424-8247/18/7/992human pluripotent stem cellsorganoidsdrug discoveryprecision medicinetoxicologypatient-derived models
spellingShingle Eleanor Luce
Jean-Charles Duclos-Vallee
Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine
Pharmaceuticals
human pluripotent stem cells
organoids
drug discovery
precision medicine
toxicology
patient-derived models
title Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine
title_full Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine
title_fullStr Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine
title_full_unstemmed Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine
title_short Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine
title_sort stem cells and organoids a paradigm shift in preclinical models toward personalized medicine
topic human pluripotent stem cells
organoids
drug discovery
precision medicine
toxicology
patient-derived models
url https://www.mdpi.com/1424-8247/18/7/992
work_keys_str_mv AT eleanorluce stemcellsandorganoidsaparadigmshiftinpreclinicalmodelstowardpersonalizedmedicine
AT jeancharlesduclosvallee stemcellsandorganoidsaparadigmshiftinpreclinicalmodelstowardpersonalizedmedicine