New Platforms For Drug Screening And Toxicology: Necessity Or Need?

Heydari, Zahra; Vosough, Massoud

doi:10.30699/mmlj17.1.3.107

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…Updated methods that aim to maintain the primary characteristics in isolated PHHs commonly focus on hepatic microenvironment recapitulation by mimicking cell-cell and cell-matrix interactions [3,4]. An ideal model would consider PHH interactions with the supporting stromal cells, extracellular matrix (ECM), and soluble factors [5,6]. The cell-cell junctions and cell-matrix connections regulate PHH polarization, which is crucial for maintenance of functionality [7,8].…”

Section: Introductionmentioning

confidence: 99%

Biofabrication of size-controlled liver microtissues incorporated with ECM-derived microparticles to prolong hepatocyte function

et al. 2021

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Multicellular microtissues of primary human hepatocytes (PHHs) co-cultured with other supporting cell types are a promising model for drug screening and toxicological studies. However, these liver microtissues (LMs) rapidly lose their functions during ex vivo culture. Here, in order to mimic the cellular and structural hepatic microenvironment, we co-cultured PHHs with human mesenchymal stromal cells (MSCs) and human umbilical vein endothelial cells (HUVECs) in the presence of cell-sized microparticles (MPs) derived from liver extracellular matrix (LEMPs). The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues (PHH:HUVEC:MSC = 3:2:1) with efficient LEMP incorporation (about 70% at a 2:1 ratio of cells:MP). The biofabricated liver microtissues (BLMs) were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression, functional activity, cytochrome P450 (CYP450) enzyme inducibility, and drug sensitivity. The results supported superior hepatic-related gene expression, functional activity, and polarity for PHH in BLM compared to LM. CYP450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM group. In conclusion, microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation applications. In the near future, this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.

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Section: Introductionmentioning

confidence: 99%

Biofabrication of size-controlled liver microtissues incorporated with ECM-derived microparticles to prolong hepatocyte function

et al. 2021

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Organoids: a novel modality in disease modeling

et al. 2021

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Graphic abstract Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately. Recent advances in the improvement of protocols have resulted in establishing three-dimensional (3D) organ-like architectures called ‘organoids’ that can display the characteristics of their corresponding real organs, including morphological features, functional activities, and personalized responses to specific pathogens. We discuss different organoid-based 3D models herein, which are classified based on their original germinal layer. Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies, including drug screening, toxicology, and molecular pathophysiology of diseases. This paper also outlines the key challenges, advantages, and prospects of current organoid systems.

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