3D Miniaturization of Human Organs for Drug Discovery

Park, Joseph; Wetzel, Isaac; Dréau, Didier; Cho, Hansang

doi:10.1002/adhm.201700551

Cited by 38 publications

(43 citation statements)

References 171 publications

(248 reference statements)

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“…On the other hand, as the tumor organoids lost their original arrangement style, it was necessary to develop new technology such as scaffolds, 3D printing technology, and air-liquid interface, which facilitated tumor organoids form similar structures to primary tumor tissues. 3D printing technology had been used to construct an engineered organ, which enabled the organ to complete the spatial arrangement of cells, the composition of ECM, and the multicellular activity [ 103 , 104 ]. In 3D scaffolds, cancer cells and endothelial cells were co-cultured, a vascular structure could be formed by using microfluidic technology [ 105 ].…”

Section: The Deficiency and Prospect Of Cancer Organoid Model For Drumentioning

confidence: 99%

Drug screening model meets cancer organoid technology

Liu

Qin

Huang

et al. 2020

Translational Oncology

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Tumor organoids inherit the genomic and molecular characteristics of the donor tumor, which not only bridge the gap between genome and phenotype but also circumvent the disadvantages such as genetic information change by using 2D cell lines and the mouse-specific tumor evolution in patient-derived xenograft (PDX). So, cancer organoid has been widely applied to preclinical drug evaluation, biomarker identification, biological research, and individualized therapy. Besides, cancer organoid can be preserved, resuscitated, passed infinitely, and mechanically cultured on a chip for drug screening; it has become one of the partial models for low/high-throughput drug screening in the preclinical trial in vitro. Therefore, this review presents the recent developments of tumor organoids for drug screening, which will introduce from four aspects, including the stability/credibility, types, application, deficiency and prospect of the tumor organoids model for drug screening.

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Section: The Deficiency and Prospect Of Cancer Organoid Model For Drumentioning

confidence: 99%

Drug screening model meets cancer organoid technology

Liu

Qin

Huang

et al. 2020

Translational Oncology

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“…Conventional approaches to produce cell aggregates, including culturing cell in stirring suspension 11 , round bottom non-adherent plate 12 , by magnetic levitation 13 , and hanging drop 14 , are hampered by the limitations like the variation in spheroids size, cell number, labor-intensive, high-shear force, and difficulties on massive production 15 . Recently, some microfabrication based methods, such as microwell 16–18 , microfluidics 19,20 , and microfabricated hanging drop 21–23 , have gained lots of attention due to the formation of a large amount of well-controlled aggregates with uniform size, less laborious, and amenable to high throughput screening 24 . However, to produce such platforms, expensive and time-consuming photolithography or micro-molding fabrication is still an indispensable requisite in those methodologies, and thus are closed-source technologies and not a cost-effective way to perform a micro tissue-based assay.…”

Section: Introductionmentioning

confidence: 99%

A 3D Printed Hanging Drop Dripper for Tumor Spheroids Analysis Without Recovery

Zhao

Xiu

Liu

et al. 2019

Sci Rep

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Compared with traditional monolayer cell culture, the three-dimensional tumor spheroid has emerged as an essential in vitro model for cancer research due to the recapitulation of the architecture and physiology of solid human tumors. Herein, by implementing the rapid prototyping of a benchtop 3D printer, we developed a new strategy to generate and analyze tumor spheroids on a commonly used multi-well plate. In this method, the printed artifact can be directly mounted on a 96/384-well plate, enables hanging drop-based spheroid formation, avoiding the tedious fabrication process from micromechanical systems. Besides long-term spheroid culture (20 days), this method supports subsequent analysis of tumor spheroid by seamlessly dripping from the printed array, thereby eliminating the need for spheroids retrieval for downstream characterization. We demonstrated several tumor spheroid-based assays, including tumoroid drug testing, metastasis on or inside extracellular matrix gel, and tumor transendothelial (TEM) assay. Based on quantitative phenotypical and molecular analysis without any precarious retrieval and transfer, we found that the malignant breast cancer (MDA-MB-231) cell aggregate presents a more metastatic morphological phenotype than the non-malignant breast cancer (MCF-7) and colonial cancer (HCT-116) cell spheroid, and shows an up-regulation of epithelial-mesenchymal transition (EMT) relevant genes (fold change > 2). Finally, we validated this tumor malignancy by the TEM assay, which could be easily performed using our approach. This methodology could provide a useful workflow for expediting tumoroid modeled in vitro assay, allowing the “Lab-on-a-Cloud” scenario for routine study.

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“…Organoids can also be generated from patients with various pathological conditions, such as inflammatory bowel disease or from individuals with various genetic backgrounds (Dekkers et al 2013;VanDussen et al 2015). Organoids from individuals with cells of varying genetic make-up opens a plethora of possibilities for designing of idiosyncratic therapies and personalized medicine (reviewed in Park et al 2018;Lehle et al 2019). Nonetheless, there are disadvantages associated with the physical organization of organoids.…”

Section: Structure and Cellular Phenotypes Of Small Intestinal Epithementioning

confidence: 99%

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays

Markus¹,

Landry

Stevens

et al. 2020

In Vitro Cell.Dev.Biol.-Animal

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The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized intestinal tissue models in vitro that reflect the architecture and physiology of the gut has been a challenge for decades and the lack of translational models that predict human responses has impeded research in the drug absorption, metabolism, and drug-induced gastrointestinal toxicity space. Often, animals fail to recapitulate human physiology and do not predict human outcomes. Also, certain human pathogens are species specific and do not infect other hosts. Concerns such as variability of results, a low throughput format, and ethical considerations further complicate the use of animals for predicting the safety and efficacy xenobiotics in humans. These limitations necessitate the development of in vitro 3D human intestinal tissue models that recapitulate in vivo-like microenvironment and provide more physiologically relevant cellular responses so that they can better predict the safety and efficacy of pharmaceuticals and toxicants. Over the past decade, much progress has been made in the development of in vitro intestinal models (organoids and 3D-organotypic tissues) using either inducible pluripotent or adult stem cells. Among the models, the MatTek's intestinal tissue model (EpiIntestinal™ Ashland, MA) has been used extensively by the pharmaceutical industry to study drug permeation, metabolism, drug-induced GI toxicity, pathogen infections, inflammation, wound healing, and as a predictive model for a clinical adverse outcome (diarrhea) to pharmaceutical drugs. In this paper, our review will focus on the potential of in vitro small intestinal tissues as preclinical research tool and as alternative to the use of animals.

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3D Miniaturization of Human Organs for Drug Discovery

Cited by 38 publications

References 171 publications

Drug screening model meets cancer organoid technology

Drug screening model meets cancer organoid technology

A 3D Printed Hanging Drop Dripper for Tumor Spheroids Analysis Without Recovery

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays

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