Biomarkers for simplifying HTS 3D cell culture platforms for drug discovery: the case for cytokines

Lai, Yinzhi; Asthana, Amish; Kisaalita, William S.

doi:10.1016/j.drudis.2011.01.009

Cited by 38 publications

(34 citation statements)

References 33 publications

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“…A suitable matrix with proper ECM proteins and biophysical properties is required to act as a scaffolding for physical support of the cells. The enteroid culture system fulfills both requirements enabling expansion of human small intestinal stem cells in vitro [35]; however, the system yields 3D enteroids rather than the exposed 2D monolayer covering the intestinal surface probably due to the extremely low stiffness of the Matrigel (Young’s modulus = 50 Pa [67]).…”

Section: Discussionmentioning

confidence: 99%

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

et al. 2017

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The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function.

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Section: Discussionmentioning

confidence: 99%

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

et al. 2017

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“…71 Others seek simply to develop a reproducible 3D cell culture platform for high throughput screening through the identification and validation of ubiquitous three-dimensionality biomarkers, such as the cytokine family. 72 Table 2 summaries the key advantages and disadvantages of 3D cell culture systems for applications in drug discovery.…”

Section: D Cell Cultures In Drug Discoverymentioning

confidence: 99%

Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors

Edmondson

Broglie

Adcock

et al. 2014

ASSAY and Drug Development Technologies

1,954

1,736

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Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review.

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“…Many studies have highlighted the importance of the 3D cell culture systems in inducing a differential gene and protein expression for several cell lines (Zschenker et al 2012). This if of significance is in utilizing this differential expression for cancer research and biomarker discovery (Bazou 2010;Lai et al 2011). …”

Section: Introductionmentioning

confidence: 99%

Culture phases, cytotoxicity and protein expressions of agarose hydrogel induced Sp2/0, A549, MCF-7 cell line 3D cultures

2014

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Advancements in cell cultures are occurring at a rapid pace, an important direction is culturing cells in 3D conditions. We demonstrate the usefulness of agarose hydrogels in obtaining 3 dimensional aggregates of three cell lines, A549, MCF-7 and Sp2/0. The differences in culture phases, susceptibility to cisplatin-induced cytotoxicity are studied. Also, the 3D aggregates of the three cell lines were reverted into 2D cultures and the protein profile differences among the 2D, 3D and revert cultures were studied. The analysis of protein profile differences using UniProt data base further augment the usefulness of agarose hydrogels for obtaining 3D cell cultures.

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Biomarkers for simplifying HTS 3D cell culture platforms for drug discovery: the case for cytokines

Cited by 38 publications

References 33 publications

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors

Culture phases, cytotoxicity and protein expressions of agarose hydrogel induced Sp2/0, A549, MCF-7 cell line 3D cultures

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