<i>In vitro</i> functional models for human liver diseases and drug screening: beyond animal testing

Paradiso, Alessia; Volpi, Marina; Rinoldi, Chiara; Celikkin, Nehar; Negrini, Nicola Contessi; Bilgen, Muge; Dallera, Giorgio; Pierini, Filippo; Costantini, Marco; Święszkowski, Wojciech; Farè, Silvia

doi:10.1039/d1bm01872h

Cited by 14 publications

(5 citation statements)

References 245 publications

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“…Chronic diseases present unique challenges for 3D in vitro models due to their multifaceted nature. 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 ).…”

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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“…While there have been recent advances in scalable 3D liver scaffolds for drug metabolism and toxicology studies, standardized test platforms aimed at replacing animal models are still in the early stages. The main challenge lies in the lack of accurate methods for specific predictions and the repeatability of data-driven results . The newly developed liver model not only demonstrates high predictability but also scalability, making it easily adaptable to high-throughput drug screening and implantation research.…”

Section: Vascularized Organ-on-a-chipmentioning

confidence: 99%

From Organ-on-a-Chip to Human-on-a-Chip: A Review of Research Progress and Latest Applications

Huang,

Liu,

Huang

et al. 2024

ACS Sens.

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Organ-on-a-Chip (OOC) technology, which emulates the physiological environment and functionality of human organs on a microfluidic chip, is undergoing significant technological advancements. Despite its rapid evolution, this technology is also facing notable challenges, such as the lack of vascularization, the development of multiorgan-on-a-chip systems, and the replication of the human body on a single chip. The progress of microfluidic technology has played a crucial role in steering OOC toward mimicking the human microenvironment, including vascularization, microenvironment replication, and the development of multiorgan microphysiological systems. Additionally, advancements in detection, analysis, and organoid imaging technologies have enhanced the functionality and efficiency of Organs-on-Chips (OOCs). In particular, the integration of artificial intelligence has revolutionized organoid imaging, significantly enhancing high-throughput drug screening. Consequently, this review covers the research progress of OOC toward Human-on-achip, the integration of sensors in OOCs, and the latest applications of organoid imaging technologies in the biomedical field.

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“…The liver is a special organ that performs a variety of tasks, including the metabolism of glucose, detoxification, urea generation, and secretion. , Although the liver can greatly replenish itself in the body, maintaining hepatocytes in vitro has proven challenging. Coculturing hepatocytes with other types of cells has been proven to increase the stabilization and maintenance of liver-specific function.…”

Section: Overview Of Different Techniques For Coculturing Cellsmentioning

confidence: 99%

Generation of Patterned Cocultures in 2D and 3D: State of the Art

Joshi,

Singh

2023

ACS Omega

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Cells inside the body are embedded into a highly structured microenvironment that consists of cells that lie in direct or close contact with other cell types that regulate the overall tissue function. Therefore, coculture models are versatile tools that can generate tissue engineering constructs with improved mimicking of in vivo conditions. While there are many reviews that have focused on pattering a single cell type, very few reviews have been focused on techniques for coculturing multiple cell types on a single substrate with precise control. In this regard, this Review covers various technologies that have been utilized for the development of these patterned coculture models while mentioning the limitations associated with each of them. Further, the application of these models to various tissue engineering applications has been discussed.

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In vitro functional models for human liver diseases and drug screening: beyond animal testing

Abstract: Liver is one of the most important and complex organs in the human body, being characterized by a sophisticated microarchitecture and responsible for key physiological functions. Despite its remarkable ability...

Cited by 14 publications

References 245 publications

Designer cellular spheroids with DNA origami for drug screening

Designer cellular spheroids with DNA origami for drug screening

From Organ-on-a-Chip to Human-on-a-Chip: A Review of Research Progress and Latest Applications

Generation of Patterned Cocultures in 2D and 3D: State of the Art

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