Three-Dimensional Cell Cultures in Drug Discovery and Development

Ye, Fang; Eglen, Richard M.

doi:10.1177/1087057117696795

Cited by 651 publications

(460 citation statements)

References 146 publications

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“…Conversely, although conventional 2D models of cells cultured in Transwell plates provide the opportunity to incorporate host components and easy access to manipulating culturing parameters, they are unable to replicate 3D organ structure, integrate physiological functions and present in vivo environmental conditions such as blood vessel fluid flow, shear stress and cyclic stress/stretch [164,265]. As a result, improvements have been made in an effort to not only provide a simplified platform for culturing tissue-like and even organ-like structures, but also to successfully replicate the functionality of human organ systems and their microenvironments [53,266,267].…”

Section: Summary and Future Outlookmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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A B S T R A C TBacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections. Lack of adequate model systemsCommonly, a variety of inconsistent, in vitro and in vivo models have been progressively utilized for antibiotic/drug development and pathophysiological studies. These systems range from simple in vitro models using microtiter plate assays and flow cells to more complex in https://doi.

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Section: Summary and Future Outlookmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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“…All the organoid characteristics make these models less amenable to high-throughput screening/high-content screening and are responsible for the complications in in vitro assays (Fang & Eglen, 2017). On the contrary, spheroids are more compliant with high-throughput screening/high-content screening because they are characterized by easy-to-use protocols and scalable culture methods (co-culture or monoculture) with high reproducibility (Fang & Eglen, 2017).…”

Section: Main Advantages Disadvantages and Limitations Of Organoidmentioning

confidence: 99%

Organoids are promising tools for species‐specific in vitro toxicological studies

Augustyniak

Bertero

Coccini³

et al. 2019

J of Applied Toxicology

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Organoids are three‐dimensional self‐aggregating structures generated from stem cells (SCs) or progenitor cells in a process that recapitulates molecular and cellular stages of early organ development. The differentiation process leads to the appearance of specialized mature cells and is connected with changes in the organoid internal structure rearrangement and self‐organization. The formation of organ‐specific structures in vitro with highly ordered architecture is also strongly influenced by the extracellular matrix. These features make organoids as a powerful model for in vitro toxicology. Nowadays this technology is developing very quickly. In this review we present, from a toxicological and species‐specific point of view, the state of the art of organoid generation from adult SCs and pluripotent SCs: embryonic SCs or induced pluripotent SCs. The current culture organoid techniques are discussed for their main advantages, disadvantages and limitations. In the second part of the review, we concentrated on the characterization of species‐specific organoids generated from tissue‐specific SCs of different sources: mammary (bovine), epidermis (canine), intestinal (porcine, bovine, canine, chicken) and liver (feline, canine).

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“…Moreover, synthetic biomaterials, like RADA‐16, have added binding sites potentially activating adhesion pathways, making all these hydrogels interesting for in vitro adhesion studies . In 3D neuronal cultures, a lack of tissue mimicry associated with the 3D architecture and degrees of freedom and the immature stage of hPSC‐derived neurons are two main challenges that more careful studies on cell adhesion may help overcome . There are several studies in which biomaterials for human neuronal cells have been screened; however, the best is yet to be discovered.…”

Section: Introductionmentioning

confidence: 99%

Screening of Hydrogels for Human Pluripotent Stem Cell–Derived Neural Cells: Hyaluronan‐Polyvinyl Alcohol‐Collagen‐Based Interpenetrating Polymer Network Provides an Improved Hydrogel Scaffold

Ylä‐Outinen

Harju

Joki

et al. 2019

Macromolecular Bioscience

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There is a clear need for novel in vitro models, especially for neuronal applications. Development of in vitro models is a multiparameter task consisting of cell‐, biomaterial‐, and environment‐related parameters. Here, three different human origin neuronal cell sources are studied and cultured in various hydrogel 3D scaffolds. For the efficient evaluation of complex results, an indexing method for data is developed and used in principal component analysis (PCA). It is found that no single hydrogel is superior to other hydrogels, and collagen I (Col1) and hyaluronan–poly(vinyl alcohol) (HA1‐PVA) gels are combined into an interpenetrating network (IPN) hydrogel. The IPN gel combines cell supportiveness of the collagen gel and stability of the HA1‐PVA gel. Moreover, cell adhesion is studied in particular and it is found that adhesion of neurons differs from that observed for fibroblasts. In conclusion, the HA1‐PVA‐col1 hydrogel is a suitable scaffold for neuronal cells and supports adhesion formation in 3D.

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Three-Dimensional Cell Cultures in Drug Discovery and Development

Cited by 651 publications

References 146 publications

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Organoids are promising tools for species‐specific in vitro toxicological studies

Screening of Hydrogels for Human Pluripotent Stem Cell–Derived Neural Cells: Hyaluronan‐Polyvinyl Alcohol‐Collagen‐Based Interpenetrating Polymer Network Provides an Improved Hydrogel Scaffold

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