Beyond the hype and toward application: liver complex in vitro models in preclinical drug safety

被引:6
作者
Jadalannagari, Sushma [1 ,2 ]
Ewart, Lorna [1 ]
机构
[1] Emulate Inc, Dept Bioinnovat, Boston, MA USA
[2] Emulate Inc, Dept Bioinnovat, 27 Drydock Ave, Boston, MA 02210 USA
关键词
Microphysiological systems; organ-on-a-chip; preclinical risk assessment; complex in vitro models; drug-induced liver injury; predictive toxicology; Liver; CELL-DERIVED CARDIOMYOCYTES; CONGESTIVE-HEART-FAILURE; INDUCED CARDIOTOXICITY; AMPHOTERICIN-B; QT INTERVAL; CHEMOTHERAPEUTIC-AGENTS; OXIDATIVE DAMAGE; CARDIAC SAFETY; RISK; MECHANISMS;
D O I
10.1080/17425255.2024.2328794
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
IntroductionDrug induced Liver-Injury (DILI) is a leading cause of drug attrition and complex in vitro models (CIVMs), including three dimensional (3D) spheroids, 3D bio printed tissues and flow-based systems, could improve preclinical prediction. Although CIVMs have demonstrated good sensitivity and specificity in DILI detection their adoption remains limited.Areas coveredThis article describes DILI, the challenges with its prediction and the current strategies and models that are being used. It reviews data from industry-FDA collaborations and strategic partnerships and finishes with an outlook of CIVMs in preclinical toxicity testing. Literature searches were performed using PubMed and Google Scholar while product information was collected from manufacturer websites.Expert OpinionLiver CIVMs are promising models for predicting DILI although, a decade after their introduction, routine use by the pharmaceutical industry is limited. To accelerate their adoption, several industry-regulator-developer partnerships or consortia have been established to guide the development and qualification. Beyond this, liver CIVMs should continue evolving to capture greater immunological mimicry while partnering with computational approaches to deliver systems that change the paradigm of predicting DILI
引用
收藏
页码:607 / 619
页数:13
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