Pathophysiologically relevant in vitro tumor models for drug screening

Das, Viswanath; Bruzzese, Francesca; Konečný, Petr; Iannelli, Federica; Budillon, Alfredo; Hajdúch, Marián

doi:10.1016/j.drudis.2015.04.004

Cited by 48 publications

(38 citation statements)

References 64 publications

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“…Coarsely, 3D-in vitro models can be divided into matrixsupported and matrix-free models (Wang et al, 2014). Amongst others, hydrogels, decellularized matrices, porous polymers, and nanofibers might serve as scaffolds in static or dynamic experimental setups can be designed (Das et al, 2015;Carvalho et al, 2017), e.g., in organ-on-a-chip systems (Bauer et al, 2018;Hübner et al, 2018). With respect to matrix-free 3D cultures, spheroids are common due to their ease and reliability of production.…”

Section: Introductionmentioning

confidence: 99%

Routine Optical Clearing of 3D-Cell Cultures: Simplicity Forward

Nürnberg

Vitacolonna

Klicks

et al. 2020

Front. Mol. Biosci.

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Three-dimensional cell cultures, such as spheroids and organoids, serve as increasingly important models in fundamental and applied research and start to be used for drug screening purposes. Optical tissue clearing procedures are employed to enhance visualization of fluorescence-stained organs, tissues, and three-dimensional cell cultures. To get a more systematic overview about the effects and applicability of optical tissue clearing on three-dimensional cell cultures, we compared six different clearing/embedding protocols on seven types of spheroid-and chip-based threedimensional cell cultures of approximately 300 µm in size that were stained with nuclear dyes, immunofluorescence, cell trackers, and cyan fluorescent protein. Subsequent whole mount confocal microscopy and semi-automated image analysis were performed to quantify the effects. Quantitative analysis included fluorescence signal intensity and signal-to-noise ratio as a function of z-depth as well as segmentation and counting of nuclei and immunopositive cells. In general, these analyses revealed five key points, which largely confirmed current knowledge and were quantified in this study. First, there was a massive variability of effects of different clearing protocols on sample transparency and shrinkage as well as on dye quenching. Second, all tested clearing protocols worked more efficiently on samples prepared with one cell type than on co-cultures. Third, z-compensation was imperative to minimize variations in signal-tonoise ratio. Fourth, a combination of sample-inherent cell density, sample shrinkage, uniformity of signal-to-noise ratio, and image resolution had a strong impact on data segmentation, cell counts, and relative numbers of immunofluorescence-positive cells. Finally, considering all mentioned aspects and including a wish for simplicity and speed of protocols-in particular, for screening purposes-clearing with 88% Glycerol appeared to be the most promising option amongst the ones tested.

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Section: Introductionmentioning

confidence: 99%

Routine Optical Clearing of 3D-Cell Cultures: Simplicity Forward

Nürnberg

Vitacolonna

Klicks

et al. 2020

Front. Mol. Biosci.

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“…3 Polymers, such as hydrogels, possess the ability to reduce severe side effects of chemotherapeutic drugs and many of them are easy to operate and cause minimal trauma. [4][5][6][7] In recent years, silk fibroin hydrogels have been widely utilized in biomedical fields such as tissue regeneration and drug sustained release, owing to their good biocompatibility, thermal stability and controllable mechanical properties. [8][9][10] A kind of thermosensitive injectable hydrogel was prepared with hydroxypropyl cellulose (HPC) and silk fibroin (SF).…”

Section: Introductionmentioning

confidence: 99%

<p>Antitumor Activity of Thermosensitive Hydrogels Packaging Gambogic Acid Nanoparticles and Tumor-Penetrating Peptide iRGD Against Gastric Cancer</p>

Zhang¹,

Chu²,

Hu³

et al. 2020

IJN

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Introduction: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumorpenetrating peptide iRGD could improve the anti-tumor activity. Methods: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size. Results: The thermo-sensitive properties of hydrogels were characterized by 3-4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased. Discussion: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.

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“…Особенно широко они применяются при токсикологических исследованиях для выявления потенциально опасных для здоровья человека соединений, а также для изучения характера воздействия исследуемого вещества на живой организм, оценки возможных рисков и установления критической дозы. Однако в последние десятилетия более актуальными становятся исследования, основанные на клеточных технологиях [1,2,3,4]. Работа с клеточной культурой, по сравнению с использованием животных, имеет ряд очевидных преимуществ, таких как отсутствие затрат на содержание животных, уменьшение длительности эксперимента, непосредственное наблюдение цитологического воздействия, возможность исследования механизмов, опосредующих токсический эффект тестируемого вещества, на клеточном уровне [5,6,7], а также возможность использования культур клеток человека, что позволяет нивелировать межвидовые различия на молекулярно-генетическом и рецепторно-сигнальном уровнях [5,6,8].…”

Section: Introductionunclassified

Assessment of Potential Cytotoxicity During Vital Observation at the BioStation CT

Trukhan

Dremina

Lozovskaya

et al. 2019

Acta biomedica scientifica

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In recent decades, the methods based on the cell technologies have become more relevant for medical and pharmaceutical research. In this paper, weconsidered the BioStation CT using for continuous in vivo observation of Ehrlich ascitic carcinoma cell culture under the influence of two active substances in different concentrations (from 1.25 to 20 mg/l). As a result of the carcinoma cells condition monitoring for 4.5 days it was shown that substance No 2 does not affect the cell viability while substance No 1 causes the carcinoma cell death, and this active substance effect is dose-dependent. Photodocumentation at two-hour intervals allowed us to research differences in the rate of cell destruction (intensive disintegration in the first day with further stabilization of the living cells number or gradual cell death throughout the experiment), as well as differences in the time of 50 % mortality reaching. Thus in the study it was demonstrated that due to the fact that the BioStation CT combines the properties of a CO2 -incubator and a microscope this device is promising for toxicological studies and significantly expands the detection possibilities of processes occurring with living cells for a sufficiently long time period making possible further analysis of the cell behavior characteristics throughout the experiment, and that is fundamentally different from the systems allowing only the final result fixation of long-term active substance exposure.

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Pathophysiologically relevant in vitro tumor models for drug screening

Cited by 48 publications

References 64 publications

Routine Optical Clearing of 3D-Cell Cultures: Simplicity Forward

Routine Optical Clearing of 3D-Cell Cultures: Simplicity Forward

<p>Antitumor Activity of Thermosensitive Hydrogels Packaging Gambogic Acid Nanoparticles and Tumor-Penetrating Peptide iRGD Against Gastric Cancer</p>

Assessment of Potential Cytotoxicity During Vital Observation at the BioStation CT

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