Modelling fatty liver disease with mouse liver-derived multicellular spheroids

Os, Elise Anne van; Cools, Laura; Eysackers, Nathalie; Smout, Ayla; Verhulst, Stefaan; Reynaert, Hendrik; McCourt, Peter; Mannaerts, Inge; Grunsven, Leo A. van

doi:10.1016/j.biomaterials.2022.121817

Cited by 10 publications

(6 citation statements)

References 54 publications

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“…Accurately portraying progressive chronic diseases, particularly those involving multiple stages, necessitates intricate interactions among diverse cell types and spatial configurations ( 37 ). In the realm of chronic liver diseases, existing models often fall short in recreating fibrous structures typical of chronic liver diseases, affecting drug delivery and treatment efficacy ( 23 , 38 ). Addressing this gap, we harnessed the NAC strategy.…”

Section: Resultsmentioning

confidence: 99%

Designer cellular spheroids with DNA origami for drug screening

Wei,

Sun,

Wang

et al. 2024

Sci. Adv.

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Current in vitro models struggle to balance the complexity of human diseases with suitability for large-scale drug tests. While 3D cultures simulate human tissues, they lack cellular intricacy, and integrating these models with high-throughput drug screening remains a challenge. Here, we introduce a method that uses self-assembling nucleic acid nanostructures decorated living cells, termed NACs, to create spheroids with a customizable 3D layout. To demonstrate its uniqueness, our method effectively creates designer 3D spheroids by combining parenchymal cells, stromal cells, and immune cells, leading to heightened physiological relevance and detailed modeling of complex chronic diseases and immune-stromal interactions. Our approach achieves a high level of biological fidelity while being standardized and straightforward to construct with the potential for large-scale drug discovery applications. By merging the precision of DNA nanotechnology with advanced cell culture techniques, we are streamlining human-centric models, striking a balance between complexity and standardization, to boost drug screening efficiency.

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Section: Resultsmentioning

confidence: 99%

Designer cellular spheroids with DNA origami for drug screening

Wei,

Sun,

Wang

et al. 2024

Sci. Adv.

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“…They generated syngeneic multicellular organoids at a large scale and could perform proof-of-principle studies for anti-fibrotic medication candidates. 65 These data suggest that ICO assembly with stromal or immune cells may be a promising avenue to decipher the human fibroinflammatory crosstalk. Notably, epithelial intestinal or pulmonary cells were shown to mature co-cultured innate lymphoid cells into tissue-specific phenotypes without requiring subset-specific cytokine supplementation.…”

Section: Primary Tissue-derived Organoids For Nafld Studiesmentioning

confidence: 93%

Modeling Nonalcoholic Fatty Liver Disease in the Dish Using Human-Specific Platforms: Strategies and Limitations

Rezvani¹,

Vallier²,

Guillot³

2023

Cellular and Molecular Gastroenterology and Hepatology

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“…Functional multicellular hepatic globular cultures were established using mouse primary hepatocytes, hepatic stellate cells, LSECs, and Kupffer cells. 118 The development of steatosis and fibrosis in organoids can be triggered by FFAs and lipopolysaccharides 119 – 121 Liver-on-chip technology is based on microstructures and microfluid perfusion devices, aiming at building microfunctional livers. 122 Gori et al 123 cultured HepG2 cells with the addition of FFAs in a microfluidic apparatus.…”

Section: Current Experimental Models Of Nafldmentioning

confidence: 99%

Experimental models of fatty liver diseases: Status and appraisal

Wang

Shen

Seo

et al. 2023

Hepatology Communications

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Fatty liver diseases, including alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease nonalcoholic fatty liver disease (NAFLD), affect a large number of people worldwide and become one of the major causes of end-stage liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC). Unfortunately, there are currently no approved pharmacological treatments for ALD or NAFLD. This situation highlights the urgent need to explore new intervention targets and discover effective therapeutics for ALD and NAFLD. The lack of properly validated preclinical disease models is a major obstacle to the development of clinical therapies. ALD and NAFLD models have been in the development for decades, but there are still no models that recapitulate the full spectrum of ALD and NAFLD. Throughout this review, we summarize the current in vitro and in vivo models used for research on fatty liver diseases and discuss the advantages and limitations of these models.

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Modelling fatty liver disease with mouse liver-derived multicellular spheroids

Cited by 10 publications

References 54 publications

Designer cellular spheroids with DNA origami for drug screening

Designer cellular spheroids with DNA origami for drug screening

Modeling Nonalcoholic Fatty Liver Disease in the Dish Using Human-Specific Platforms: Strategies and Limitations

Experimental models of fatty liver diseases: Status and appraisal

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