Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy

Astolfi, Mélina; Péant, Benjamin; Lateef, M. A.; Rousset, Nassim; Kendall‐Dupont, Jennifer; Carmona, Eurı́dice; Monet, Frédéric; Saad, Fred; Provencher, Diane; Mes-Masson, Anne-Marie; Gervais, Thomas

doi:10.1039/c5lc01108f

Cited by 163 publications

(191 citation statements)

References 52 publications

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“…The complicated geometries of the µSFCs and the limited diffusion of glucose and oxygen to spheroids create unpredictable concentration profiles within the cultured spheroids. Thus, mathematical and numerical analyses combined with experimental investigations are needed to predict the condition of hypoxia in the spheroids [108,[112][113][114][115][116]. The microstructure-or microwell-based µSFCs have limited applications in high-throughput screening.…”

Section: Microfluidic Methods For Spheroid Culturementioning

confidence: 99%

Inventions and Innovations in Preclinical Platforms for Cancer Research

2018

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Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumour models. The complex tumour microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

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Section: Microfluidic Methods For Spheroid Culturementioning

confidence: 99%

Inventions and Innovations in Preclinical Platforms for Cancer Research

2018

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“…Reprinted from Astolfi et al (2016), under the Creative Commons Attribution 4.0 International License. 64 EdU, 5-ethynyl-2′-deoxyuridine.…”

Section: Ex Vivo Tumor Culturementioning

confidence: 99%

Mimicking Tumors: Toward More Predictive In Vitro Models for Peptide- and Protein-Conjugated Drugs

et al. 2017

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Macromolecular drug candidates and nanoparticles are typically tested in 2D cancer cell culture models, which are often directly followed by in vivo animal studies. The majority of these drug candidates, however, fail in vivo. In contrast to classical small-molecule drugs, multiple barriers exist for these larger molecules that two-dimensional approaches do not recapitulate. In order to provide better mechanistic insights into the parameters controlling success and failure and due to changing ethical perspectives on animal studies, there is a growing need for in vitro models with higher physiological relevance. This need is reflected by an increased interest in 3D tumor models, which during the past decade have evolved from relatively simple tumor cell aggregates to more complex models that incorporate additional tumor characteristics as well as patient-derived material. This review will address tissue culture models that implement critical features of the physiological tumor context such as 3D structure, extracellular matrix, interstitial flow, vascular extravasation, and the use of patient material. We will focus on specific examples, relating to peptide-and protein-conjugated drugs and other nanoparticles, and discuss the added value and limitations of the respective approaches.

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“…Thus, a platform that is designed for loading of pre-formed aggregates has greater experimental flexibility and can be used more broadly. While previous work has shown the ability to load pre-formed aggregates into devices with wells or traps, 42–46 the majority of existing platforms are low-throughput, accommodating 20 samples or less, and are not inherently scalable (e.g. the fluidics required for trapping are not compact or the trapping mechanism is not deterministic).…”

Section: Introductionmentioning

confidence: 99%

A microfluidic trap array for longitudinal monitoring and multi-modal phenotypic analysis of individual stem cell aggregates

Jackson-Holmes

McDevitt

2017

Lab Chip

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Three-dimensional pluripotent stem cell (PSC) cultures have the ability to undergo differentiation, self-organization, and morphogenesis to yield complex, in vitro tissue models that recapitulate key elements of native tissues. These tissue models offer a system for studying mechanisms of tissue development, investigating disease mechanisms, and performing drug screening. It remains challenging, however, to standardize PSC aggregate differentiation and morphogenesis methods due to heterogeneity stemming from biological and environmental sources. It is also difficult to monitor and assess large numbers of individual samples longitudinally throughout culture using typical batch-based culture methods. To address these challenges, we have developed a microfluidic platform for culture, longitudinal monitoring, and phenotypic analysis of individual stem cell aggregates. This platform uses a hydrodynamic loading principle to capture pre-formed stem cell aggregates in independent traps. We demonstrated that multi-day culture of aggregates in this platform reduces heterogeneity in phenotypic parameters such as size and morphology. Additionally, we showed that culture and analysis steps can be performed sequentially in the same platform, enabling correlation of multiple modes of analysis for individual samples. We anticipate this platform being applied to improve abilities for phenotypic analysis of PSC aggregate tissues and to facilitate research in standardizing culture systems in order to dually increase the yield and reduce the heterogeneity of PSC-derived tissues.

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Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy

Cited by 163 publications

References 52 publications

Inventions and Innovations in Preclinical Platforms for Cancer Research

Inventions and Innovations in Preclinical Platforms for Cancer Research

Mimicking Tumors: Toward More Predictive In Vitro Models for Peptide- and Protein-Conjugated Drugs

A microfluidic trap array for longitudinal monitoring and multi-modal phenotypic analysis of individual stem cell aggregates

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