Cell-cell interactions in spheroids maintained in suspension

Djordjević, Božidar; Lange, Christopher S.

doi:10.1080/02841860500520743

Cited by 33 publications

(19 citation statements)

References 27 publications

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“…They are particularly useful for mixing different populations of tumour cell lines for studying drug resistance or therapy response [32] and for mixing tumour and fibroblast cell populations to examine tumour-stromal cell interactions [33]. Mostly two cell lines are used but it is possible to use more, although this increases the complexity of the culture technique.…”

Section: Mixed Mosaic Spheroid Culturementioning

confidence: 99%

Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia

Leek

Grimes

Harris

et al. 2016

Advances in Experimental Medicine and Biology

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Regions of hypoxia in tumours can be modelled in vitro in 2D cell cultures with a hypoxic chamber or incubator in which oxygen levels can be regulated. Although this system is useful in many respects, it disregards the additional physiological gradients of the hypoxic microenvironment, which result in reduced nutrients and more acidic pH. Another approach to hypoxia modelling is to use three-dimensional spheroid cultures. In spheroids, the physiological gradients of the hypoxic tumour microenvironment can be inexpensively modelled and explored. In addition, spheroids offer the advantage of more representative modelling of tumour therapy responses compared with 2D culture. Here, we review the use of spheroids in hypoxia tumour biology research and highlight the different methodologies for spheroid formation and how to obtain uniformity. We explore the challenge of spheroid analyses and how to determine the effect on the hypoxic versus normoxic components of spheroids. We discuss the use of high-throughput analyses in hypoxia screening of spheroids. Furthermore, we examine the use of mathematical modelling of spheroids to understand more fully the hypoxic tumour microenvironment.

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Section: Mixed Mosaic Spheroid Culturementioning

confidence: 99%

Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia

Leek

Grimes

Harris

et al. 2016

Advances in Experimental Medicine and Biology

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show abstract

“…However, cancer cells growing on 2D plastic surface is an artificial cellular environment and cannot accurately mimic the 3D in vivo tumor environment [30]. These monolayer growing cells lose part of their phenotypic and functional characteristics compared to the cells in the 3D real tumors [31]. Therefore, the drug candidates identified with this assay may not be the best compounds for further in vivo studies.…”

Section: Discussionmentioning

confidence: 97%

In vitro and in vivo evaluation of tubulin inhibitors with non-small cell lung cancer pre-clinical models

Lama¹,

Liu²,

Zhong³

et al. 2015

J Cancer Res Ther

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“…The striking similarity to in vivo morphologies and behaviors of cells grown in 3-D culture environments is now well accepted [Djordjevic and Lange, 2006;Pampaloni et al, 2007;Justice et al, 2009]. However, stem cells, which may have more subtle culture requirements, offer an even greater challenge to understanding how cells grow and differentiate in response to 3-D environmental cues.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Dimensionality on Growth and Differentiation of Neural Progenitors from Different Regions of Fetal Rat Brain in vitro: 3-Dimensional Spheroid versus 2-Dimensional Monolayer Culture

Lü

Searle

Liu

et al. 2012

Cells Tissues Organs

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Three-dimensional (3-D) spheroids are widely used for culturing cells. However, 2-dimensional (2-D) monolayer cultures have also been adopted for culture and used in a broad range of cell biology studies. To address the effect of dimensionality on the growth and differentiation of neuroprogenitor cells in 3-D spheroids and 2-D monolayer cultures, cells were isolated from cerebral cortex, cerebella and brainstem of fetal rat brain then cultured in serum-free DMEM/F12 medium or DMEM with 10% FBS. The growth and differentiation of neuroprogenitor cells from three brain regions in spheroids was compared with that in monolayer cultures, and the differentiation components of neuroprogenitor cells were compared with in vivo brain sections. Neuroprogenitor cells in spheroids proliferate actively over 10 days in culture as showed by Ki67 incorporation and increase in spheroid diameter. More neuroprogenitor cells underwent neuronal differentiation in spheroids than in monolayer cultures. In comparison with fixed rat brain sections, the neuron to astrocyte ratio, as shown by neurofilament to glial fibrillary acidic protein immunoreactivity, in spheroids is similar to that found in adult rat tissue sections. Our results suggest that the spheroid culture system mimics the in vivo cytoarchitecture to a greater extent and more closely reflects the cellular composition in adult brain tissue. This supports the notion that the intercellular niche in spheroids is more favorable for the survival and differentiation of neuronal precursors, while the cues in monolayer cultures may favor glial cell survival. It is therefore concluded that dimensionality plays a significant role in determining cellular behavior in vitro.

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Cell-cell interactions in spheroids maintained in suspension

Cited by 33 publications

References 27 publications

Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia

Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia

In vitro and in vivo evaluation of tubulin inhibitors with non-small cell lung cancer pre-clinical models

The Effect of Dimensionality on Growth and Differentiation of Neural Progenitors from Different Regions of Fetal Rat Brain in vitro: 3-Dimensional Spheroid versus 2-Dimensional Monolayer Culture

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