Microfluidics‐based 3D cell culture models: Utility in novel drug discovery and delivery research

Gupta, Nilesh; Liu, Jeffrey R.; Patel, Brijeshkumar; Solomon, Deepak E.; Vaidya, Bhuvaneshwar; Gupta, Vivek

doi:10.1002/btm2.10013

Cited by 195 publications

(162 citation statements)

References 154 publications

(306 reference statements)

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“…Benien and Swami (2014), Carletti et al (2011), Carvalho et al (2016), Costa et al (2016), Gupta et al (2016), Haycock (2011), Knight and Przyborski (2015), McKee and Chaudhry (2017) Scaffold-free (spheroids) Benien and Swami (2014), Carletti et al (2011), Carvalho et al (2016), Costa et al (2016), Gupta et al (2016), Haycock (2011), Knight and Przyborski (2015), McKee and Chaudhry (2017) Scaffold-free (spheroids)…”

Section: Scaffold-based 3d Cell Culturesmentioning

confidence: 99%

“…Even so, most of these methodologies are laborious and costly, once they require high-tech equipment and techniques to produce the artificial structure in a highly reproducible manner (T. Lu et al, 2013;Sultana et al, 2015). Other disadvantages of scaffold-based 3D cell culture models for drug screening purposes are the establishment of interactions between the materials and the drugs affecting their absorption and adhesion (Asghar et al, 2015), and the difficulty to isolate/recover the cells or proteins from the structure for further assays (Gupta et al, 2016).…”

Section: Scaffold-based 3d Cell Culturesmentioning

confidence: 99%

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3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

Nunes

Barros

Costa

et al. 2018

Biotech & Bioengineering

541

445

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Three-dimensional cell culture models, such as spheroids, can be used in the process of the development of new anticancer agents because they are able to closely mimic the main features of human solid tumors, namely their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. These properties imprint to the spheroids an anticancer therapeutics resistance profile, which is similar to that displayed by human solid tumors. In this review, an overview of the drug resistance mechanisms observed in 3D tumor spheroids is provided. Furthermore, comparisons between the therapeutics resistance profile exhibited by spheroids, and 2D cell cultures are presented. Finally, examples of the therapeutic approaches that have been developed to surpass the drug resistance mechanisms exhibited by spheroids are described. HIGHLIGHTS•The suitability of 3D cell culture models for drug screening purposes is highlighted. •Spheroids and in vivo human solid tumors structural and functional similarities are emphasized.•The drug resistance mechanisms exhibited by spheroids are described.•Therapeutic approaches used to surpass spheroids' drug resistance mechanisms are described. K E Y W O R D Sdrug resistance, drugs, in vitro models, solid tumors, spheroids

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Section: Scaffold-based 3d Cell Culturesmentioning

confidence: 99%

Section: Scaffold-based 3d Cell Culturesmentioning

confidence: 99%

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

Nunes

Barros

Costa

et al. 2018

Biotech & Bioengineering

541

445

View full text Add to dashboard Cite

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“…Recent developments in this field have resulted in a diversity of three‐dimensional cell culture models and several dynamic systems with the ability to incorporate hemodynamic shear . Still, simultaneous visualization of the BBB and the associated transport through the barrier in real‐time remains a challenge .…”

Section: Introductionmentioning

confidence: 99%

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

Brown

Nowak

Bayles

et al. 2019

Bioengineering & Transla Med

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Microfluidic cellular models, commonly referred to as “organs‐on‐chips,” continue to advance the field of bioengineering via the development of accurate and higher throughput models, captivating the essence of living human organs. This class of models can mimic key in vivo features, including shear stresses and cellular architectures, in ways that cannot be realized by traditional two‐dimensional in vitro models. Despite such progress, current organ‐on‐a‐chip models are often overly complex, require highly specialized setups and equipment, and lack the ability to easily ascertain temporal and spatial differences in the transport kinetics of compounds translocating across cellular barriers. To address this challenge, we report the development of a three‐dimensional human blood brain barrier (BBB) microfluidic model (μHuB) using human cerebral microvascular endothelial cells (hCMEC/D3) and primary human astrocytes within a commercially available microfluidic platform. Within μHuB, hCMEC/D3 monolayers withstood physiologically relevant shear stresses (2.73 dyn/cm 2 ) over a period of 24 hr and formed a complete inner lumen, resembling in vivo blood capillaries. Monolayers within μHuB expressed phenotypical tight junction markers (Claudin‐5 and ZO‐1), which increased expression after the presence of hemodynamic‐like shear stress. Negligible cell injury was observed when the monolayers were cultured statically, conditioned to shear stress, and subjected to nonfluorescent dextran (70 kDa) transport studies. μHuB experienced size‐selective permeability of 10 and 70 kDa dextrans similar to other BBB models. However, with the ability to probe temporal and spatial evolution of solute distribution, μHuBs possess the ability to capture the true variability in permeability across a cellular monolayer over time and allow for evaluation of the full breadth of permeabilities that would otherwise be lost using traditional end‐point sampling techniques. Overall, the μHuB platform provides a simplified, easy‐to‐use model to further investigate the complexities of the human BBB in real‐time and can be readily adapted to incorporate additional cell types of the neurovascular unit and beyond.

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“…Complexity is obviously creating an environment that favours the interactions between a cell for sharing and propagation of important information exchange, often leading to complex and every detail very carefully planned from a target issue or cell [23]. Classic examples of such cell-based information exchange in the body include as just a few examples [24] as satellite cells (myoblasts), cardiomyocytes and cardiac pacemaker cells.…”

Section: Tissue Regenerationmentioning

confidence: 99%

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

Chaud¹,

Alves²,

Rebelo³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

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Dilated cardiomyopathy (DMC) of ischemic or non-ischemic aetiology remains a lethal condition nowadays. Despite early percutaneous or medical revascularization after an acute myocardial infarct (AMI), many patients still develop DMC and severe heart failure due to cardiac remodelling. Possibility of regenerating myocardium already damaged or at least inducing a more positive cardiac remodelling with use of biodegradable scafolds has been atempted in many experimental studies, which can be cellular or acellular. In the cellular scafolds, the cells are incorporated in the structure prior to implantation of the same into the injured tissue. Acellular scafolds, in turn, are composites that use one or more biomaterials present in the extracellular matrix (ECM), such as proteoglycans non-proteoglycan polysaccharide, proteins and glycoproteins to stimulate the chemotaxis of cellular/molecular complexes as growth factors to initiate speciic regeneration. For the development of scafold, the choice of biomaterials to be used must meet speciic biological, chemical and architectural requirements like ECM of the tissue of interest. In acute myocardial infarction, treating the root of the problem by repairing injured tissue is more beneicial to the patient. Inducing more constructive forms of endogenous repair. Thus, patches of acellular scafolds capable of mimicking the epicardium and ECM should be able to atenuate both cardiac remodelling and adverse cardiac dysfunction.

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Microfluidics‐based 3D cell culture models: Utility in novel drug discovery and delivery research

Cited by 195 publications

References 154 publications

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

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