Liver organoid as a 3D in vitro model for drug validation and toxicity assessment

Brooks, Anastasia; Liang, Xiaowen; Zhang, Yonglong; Zhao, Chunxia; Roberts, Michael S.; Wang, Haolu; Zhang, Lei; Crawford, Darrell H. G.

doi:10.1016/j.phrs.2021.105608

Cited by 48 publications

(36 citation statements)

References 94 publications

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“…Individual-specific drug responses could also be tested in these liver organoid models. Moreover, liver organoid biobanks could also serve as a platform for predicting individual-specific drug-induced liver injury, the main underlying factor in acute liver failure 162 , 163 .…”

Section: Drug Discovery and Precision Medicinementioning

confidence: 99%

Modelling metabolic diseases and drug response using stem cells and organoids

Lazar

2022

Nat Rev Endocrinol

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Metabolic diseases, including obesity, diabetes mellitus and cardiovascular disease, are a major threat to health in the modern world, but efforts to understand the underlying mechanisms and develop rational treatments are limited by the lack of appropriate human model systems. Notably, advances in stem cell and organoid technology allow the generation of cellular models that replicate the histological, molecular and physiological properties of human organs. Combined with marked improvements in gene editing tools, human stem cells and organoids provide unprecedented systems for studying mechanisms of metabolic diseases. Here, we review progress made over the past decade in the generation and use of stem cell-derived metabolic cell types and organoids in metabolic disease research, especially obesity and liver diseases. In particular, we discuss the limitations of animal models and the advantages of stem cells and organoids, including their application to metabolic diseases. We also discuss mechanisms of drug action, understanding the efficacy and toxicity of existing therapies, screening for new treatments and pursuing personalized therapies. We highlight the potential of combining stem cell-derived organoids with gene editing and functional genomics to revolutionize the approach to finding treatments for metabolic diseases.

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Section: Drug Discovery and Precision Medicinementioning

confidence: 99%

Modelling metabolic diseases and drug response using stem cells and organoids

Lazar

2022

Nat Rev Endocrinol

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“…Recent years have witnessed considerable progress of liver organoids. This culture system was applied for pharmaceutical research [42][43][44][45], precision medicine, and modeling liver disease [34,35,[45][46][47][48][49][50][51]. Additionally, liver organoids can also be used in exploring liver injury and repairing liver injury.…”

Section: History Of Liver Organoidsmentioning

confidence: 99%

Liver Organoids, Novel and Promising Modalities for Exploring and Repairing Liver Injury

Lin

et al. 2022

Stem Cell Rev and Rep

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The past decades have witnessed great advances in organoid technology. Liver is the biggest solid organ, performing multifaceted physiological functions. Nowadays, liver organoids have been applied in many fields including pharmaceutical research, precision medicine and disease models. Compared to traditional 2-dimensional cell line cultures and animal models, liver organoids showed the unique advantages. More importantly, liver organoids can well model the features of the liver and tend to be novel and promising modalities for exploring liver injury, thus finding potential treatment targets and repairing liver injury. In this review, we reviewed the history of the development of liver organoids and summarized the application of liver organoids and recent studies using organoids to explore and further repair the liver injury. These novel modalities could provide new insights about the process of liver injury. Graphical abstract

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“…For example, patient-derived tumor cells can be cultured in hydrogels and commercialized Matrigel as patient-derived tumor organoids (PDTOs). The 3D matrix maintains spatial growth characteristics, which are similar to those of the extracellular matrix (ECM) in vivo [ [16] , [17] , [18] ]. The culture of PDTOs avoids the limitations of tumor size, degree of malignancy, and ethical animal problems [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%