Facile One Step Formation and Screening of Tumor Spheroids Using Droplet‐Microarray Platform

Popova, Anna A.; Tronser, Tina; Demir, Konstantin; Haitz, P; Kuodyte, Karolina; Starkuviene, Vytaute; Wajda, Piotr; Levkin, Pavel A.

doi:10.1002/smll.201901299

Cited by 65 publications

(72 citation statements)

References 47 publications

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“…For example, the 3D tumour spheroids generated were used for drug screening with three known anti‐cancer drugs (e.g., doxorubicin, oxaliplatin and 5‐fluorouracil), thereby confirming previous results of increased resistance of cancer cells in 3D versus 2D. This technology can be adapted for studying patient‐derived cells for further investigation of the effect of several drug regimens in clinically focused applications (Popova et al, 2019).…”

Section: Bioprinting Devices For 3d Cell Culturesupporting

confidence: 70%

“…Several non‐contact dispensing modes have been developed that utilize different mechanisms to generate cell droplets. These include inkjet printing, solenoid valve assisted printing, acoustic‐enabled printing and laser‐assisted bioprinting (Atala & Yoo, 2015; Bakhshinejad & D'Souza, 2015; Bishop et al, 2017; Popova et al, 2019; Tripathi & Savio Melo, 2017). These methods can be used to generate nano‐ to microlitre volumes of cell suspension and, hence, are highly amenable to high‐throughput screening.…”

Section: Bioprinting Devices For 3d Cell Culturementioning

confidence: 99%

“…This can then be used to transfer nanolitres of liquid by merely modifying the frequency. 3D tumour spheroids for multiple cancer cell lines have been generated using such an acoustic‐enabled and pressure‐driven tool (Popova et al, 2019). For example, the 3D tumour spheroids generated were used for drug screening with three known anti‐cancer drugs (e.g., doxorubicin, oxaliplatin and 5‐fluorouracil), thereby confirming previous results of increased resistance of cancer cells in 3D versus 2D.…”

Section: Bioprinting Devices For 3d Cell Culturementioning

confidence: 99%

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Three‐dimensional in vitro cell culture devices using patient‐derived cells for high‐throughput screening of drug combinations

et al. 2020

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Drug discovery using traditional animal models is often inefficient because test animal models cannot accurately represent human responses, particularly in terms of toxicology and pathophysiology. For these reasons, there is an urgent need to develop in vitro human disease models to accelerate new drug development. This is especially the case for precision medicine, where current in vitro and ex vivo models are not sufficient to predict individual drug efficacy and safety across the enormous heterogeneity of populations and individuals. In addition, model cell lines cultured under non‐physiological conditions do not recapitulate the complex microenvironment of patient tissues. Precision medicine using patient‐derived cells and drug combination therapies may be a promising solution to overcome these limitations. Three‐dimensional (3D) cell culture models can simultaneously simulate complex in vivo tissue microenvironments and be miniaturized for large‐scale screening of drug combinations using limited available patient‐derived cells. Recently, microfluidic and microarray platforms have been developed to mimic multiple human organs and human‐specific disease states, and are becoming more commonly used in high‐throughput drug screening. Herein, we highlight the current status of microfluidic‐based 3D cell culture devices, such as organ/body‐on‐chip systems, as well as microarray‐based 3D cell culture platforms, which can be combined with patient‐derived cells. Miniaturized cell culture systems using patient‐derived cells represent promising tools for identifying new drug combinations and also biological mechanisms that underlie drug synergies.

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Section: Bioprinting Devices For 3d Cell Culturesupporting

confidence: 70%

Section: Bioprinting Devices For 3d Cell Culturementioning

confidence: 99%

Section: Bioprinting Devices For 3d Cell Culturementioning

confidence: 99%

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Three‐dimensional in vitro cell culture devices using patient‐derived cells for high‐throughput screening of drug combinations

et al. 2020

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“…Recently we developed the droplet microarray (DMA) platform, [ 25–27 ] which enables fabrication of nanoliter droplet microarrays where the shape, size and density of droplets depend on the design of hydrophilic patterns surrounded by the superhydrophobic barriers. The DMA platform enables cultivation and high throughput screening of various cell types in hundreds of individual nanoliter droplets functioning as independent miniaturized habitats.…”

Section: Figurementioning

confidence: 99%

Assembly of Multi‐Spheroid Cellular Architectures by Programmable Droplet Merging

et al. 2020

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Reproduction of native tissues in vitro is important as a tool, as it both enables investigation of fundamental biological processes, and drug and toxicity screenings. In order to closely mimic complex tissues in vitro, artificial multicellular systems are created from different cell types in spatially ordered structures or welldefined geometries in a 3D microenvironment. [1-3] These systems can be built from building blocks [4-7] such as cell sheets, [8] cell-laden microgels, [5] cell spheroids, [9] and organoids. [10,11] Precise control of cellular composition and spatial distribution of building blocks within artificial multicellular systems allows for reconstitution of native tissues in their healthy and disease state in vitro. [12] There are a number of methodologies developed for fabrication of complex 3D cell systems in vitro. [3-7,13,14] Directed assembly allows manual positioning or stacking building blocks to form 3D architectures. [15,16] Birey et al. applied this method for fusion of two forebrain organoids in order to mimic the human brain development and demonstrate inter-neuronal migration. [15] The method of directed assembly is, however, manual and not compatible with high throughput. Remote assembly, such as, acoustic node, [14,17] magnetic cell levitation, [13,18] optical tweezers, [19] or laser-guided direct writing, [20] can achieve assembly of cells or spheroids against gravity or viscous forces. Chen et al. demonstrated the assembly of hepatic organoids by an acoustic node technique, and the technique was able to achieve formation of bile canaliculi networks resembling native hepatic tissue. [17] Souza et al. used magnetic cell levitation to manipulate a glioblastoma cell spheroid, and a human astrocyte spheroid in order to create a cell invasion model. [18] These methods depend on sophisticated equipment, paramagnetic media, or introduce a risk of laser-induced cell damage. Another common strategy used to fabricate multicellular architecture is assembly of cell-laden hydrogels or microgels, [5,21,22] or cell seeding on scaffolds. [7,23] However, these biomaterial-based methods failed to provide high cell packing density. The use of artificial scaffolds or gel matrices additionally lead to disadvantages for constructing 3D tissue models due to their influence on cell-cell interactions, autocrine, and paracrine signaling. 3D printing [3] is a promising method for designing and achieving multicellular architectures, but it is relatively slow, not always compatible with high throughput and relies on printable bio-inks for maintaining 3D structure and cell viability. Artificial multicellular systems are gaining importance in the field of tissue engineering and regenerative medicine. Reconstruction of complex tissue architectures in vitro is nevertheless challenging, and methods permitting controllable and high-throughput fabrication of complex multicellular architectures are needed. Here, a facile and high-throughput method is developed based on a tunable droplet-fusion technique, allowing prog...

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“…It is compatible with microscopy‐based read‐out and related procedures including staining, fixation, and immunofluorescence protocols. We have demonstrated the use of Droplet‐Microarrays for multiple screening application of adherent and suspension cells, as well as for 3D cell culture . In a recent study, we performed a screen of nine compounds on only 100 patient‐derived chronic lymphocytic leukemia (CLL) cells per a 100 nL droplet.…”

Section: Miniaturized Systems For Dsrt On 2d Cell Culture Modelsmentioning

confidence: 99%

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

Popova

Levkin

2020

Advanced Therapeutics

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Precision or personalized medicine aims to determine an optimal therapy for each individual patient. In oncology techniques such as next generation sequencing, mRNA‐sequencing, ChIP‐sequencing, and mass spectrometry are used to perform a full molecular profiling for each patient. However, it is not always possible to determine a suitable treatment for an individual cancer based on molecular profiling, mostly due to the high level of tumor heterogeneity. In vitro drug sensitivity and resistance test (DSRT) can be performed on cancer cells or tissues obtained from a patient with a panel of anticancer compounds in order to experimentally define sensitivity and resistance of each individual cancer. In combination with molecular profiling, DSRT can provide a fuller picture about the nature of disease, allowing for finding more appropriate therapy for each individual patient. In this progress report, studies describing in vitro DSRTs on 2D and 3D cell models based on patient‐derived cells are reviewed and challenges and future steps needed for the adaptation of these systems in clinics are discussed.

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Facile One Step Formation and Screening of Tumor Spheroids Using Droplet‐Microarray Platform

Cited by 65 publications

References 47 publications

Three‐dimensional in vitro cell culture devices using patient‐derived cells for high‐throughput screening of drug combinations

Three‐dimensional in vitro cell culture devices using patient‐derived cells for high‐throughput screening of drug combinations

Assembly of Multi‐Spheroid Cellular Architectures by Programmable Droplet Merging

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

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