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Liver–Heart on chip models for drug safety

Current pre-clinical models to evaluate drug safety during the drug development process (DDP) mainly rely on traditional two-dimensional cell cultures, considered too simplistic and often ineffective, or animal experimentations, which are costly, time-consuming, and not truly representative of human...

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Autores principales: Ferrari, Erika, Rasponi, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282347/
https://www.ncbi.nlm.nih.gov/pubmed/34286172
http://dx.doi.org/10.1063/5.0048986
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author Ferrari, Erika
Rasponi, Marco
author_facet Ferrari, Erika
Rasponi, Marco
author_sort Ferrari, Erika
collection PubMed
description Current pre-clinical models to evaluate drug safety during the drug development process (DDP) mainly rely on traditional two-dimensional cell cultures, considered too simplistic and often ineffective, or animal experimentations, which are costly, time-consuming, and not truly representative of human responses. Their clinical translation thus remains limited, eventually causing attrition and leading to high rates of failure during clinical trials. These drawbacks can be overcome by the recently developed Organs-on-Chip (OoC) technology. OoC are sophisticated in vitro systems capable of recapitulating pivotal architecture and functionalities of human organs. OoC are receiving increasing attention from the stakeholders of the DDP, particularly concerning drug screening and safety applications. When a drug is administered in the human body, it is metabolized by the liver and the resulting compound may cause unpredicted toxicity on off-target organs such as the heart. In this sense, several liver and heart models have been widely adopted to assess the toxicity of new or recalled drugs. Recent advances in OoC technology are making available platforms encompassing multiple organs fluidically connected to efficiently assess and predict the systemic effects of compounds. Such Multi-Organs-on-Chip (MOoC) platforms represent a disruptive solution to study drug-related effects, which results particularly useful to predict liver metabolism on off-target organs to ultimately improve drug safety testing in the pre-clinical phases of the DDP. In this review, we focus on recently developed liver and heart on chip systems for drug toxicity testing. In addition, MOoC platforms encompassing connected liver and heart tissues have been further reviewed and discussed.
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spelling pubmed-82823472021-07-19 Liver–Heart on chip models for drug safety Ferrari, Erika Rasponi, Marco APL Bioeng Reviews Current pre-clinical models to evaluate drug safety during the drug development process (DDP) mainly rely on traditional two-dimensional cell cultures, considered too simplistic and often ineffective, or animal experimentations, which are costly, time-consuming, and not truly representative of human responses. Their clinical translation thus remains limited, eventually causing attrition and leading to high rates of failure during clinical trials. These drawbacks can be overcome by the recently developed Organs-on-Chip (OoC) technology. OoC are sophisticated in vitro systems capable of recapitulating pivotal architecture and functionalities of human organs. OoC are receiving increasing attention from the stakeholders of the DDP, particularly concerning drug screening and safety applications. When a drug is administered in the human body, it is metabolized by the liver and the resulting compound may cause unpredicted toxicity on off-target organs such as the heart. In this sense, several liver and heart models have been widely adopted to assess the toxicity of new or recalled drugs. Recent advances in OoC technology are making available platforms encompassing multiple organs fluidically connected to efficiently assess and predict the systemic effects of compounds. Such Multi-Organs-on-Chip (MOoC) platforms represent a disruptive solution to study drug-related effects, which results particularly useful to predict liver metabolism on off-target organs to ultimately improve drug safety testing in the pre-clinical phases of the DDP. In this review, we focus on recently developed liver and heart on chip systems for drug toxicity testing. In addition, MOoC platforms encompassing connected liver and heart tissues have been further reviewed and discussed. AIP Publishing LLC 2021-07-14 /pmc/articles/PMC8282347/ /pubmed/34286172 http://dx.doi.org/10.1063/5.0048986 Text en © 2021 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Reviews
Ferrari, Erika
Rasponi, Marco
Liver–Heart on chip models for drug safety
title Liver–Heart on chip models for drug safety
title_full Liver–Heart on chip models for drug safety
title_fullStr Liver–Heart on chip models for drug safety
title_full_unstemmed Liver–Heart on chip models for drug safety
title_short Liver–Heart on chip models for drug safety
title_sort liver–heart on chip models for drug safety
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282347/
https://www.ncbi.nlm.nih.gov/pubmed/34286172
http://dx.doi.org/10.1063/5.0048986
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