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Macromolecular crowding effect on cartilaginous matrix production: a comparison of two-dimensional and three-dimensional models.

ABSTRACT: Macromolecular crowding (MMC) has been shown to have a beneficial effect on production and maturation of extracellular matrices in a monolayer cell culture model. To explore its potential in tissue engineering, a mixture of Ficoll 70 and Ficoll 400 is used to examine its MMC effect on cartilaginous matrix production of monolayer cultured porcine chondrocytes as well as on in vitro engineered cartilage formation using porcine chondrocytes and polyglycolic acid-unwoven fibers. The results showed that the production of total collagens and glycosaminoglycans production was enhanced by MMC in monolayer cultured cells (two-dimensional model), but the matrix production and tissue formation were significantly inhibited in the in vitro engineered cartilage (three-dimensional model) by the macromolecules. Further mechanism study on this phenomenon will be important for MMC applications in regenerative medicine.

SUBMITTER: Chen B

PROVIDER: S-EPMC3689930 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Macromolecular crowding effect on cartilaginous matrix production: a comparison of two-dimensional and three-dimensional models.

Chen Bo B Wang Bin B Zhang Wen Jie WJ Zhou Guangdong G Cao Yilin Y Liu Wei W

Tissue engineering. Part C, Methods 20130219 8

Macromolecular crowding (MMC) has been shown to have a beneficial effect on production and maturation of extracellular matrices in a monolayer cell culture model. To explore its potential in tissue engineering, a mixture of Ficoll 70 and Ficoll 400 is used to examine its MMC effect on cartilaginous matrix production of monolayer cultured porcine chondrocytes as well as on in vitro engineered cartilage formation using porcine chondrocytes and polyglycolic acid-unwoven fibers. The results showed t ...[more]

PMID: 23421450

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Project description:High cancer drug development attrition rates have provoked considerable debate about whether the two-dimensional tumor growth inhibition high-throughput screening assays used in pre-clinical lead discovery adequately reflect solid tumor complexity. We used automated high-content screening image acquisition and analysis methods to compare fluorescent drug uptake, accumulation, and distribution in Cal33 and FaDu head and neck cancer (HNC) monolayer and multicellular tumor spheroid (MCTS) models. Ellipticine, idarubicin, daunorubicin, and doxorubicin were studied because of their fluorescent properties and broad anti-tumor activities. HNC MCTSs were generated in 384-well ultra-low attachment plates where compound exposure, image acquisition, and analysis could be performed in situ. Fluorescent drug accumulation in Cal33 monolayer and MCTS cultures was linear with respect to concentration, and appeared to achieve steady-state levels within 10-15 min of drug exposure, which were maintained through 30-45 min. Drug accumulation in monolayers was independent of cell number and/or density, and every cell achieved uniform drug concentrations. In MCTSs, however, drug accumulation increased as the number of cells and sizes of the MCTSs became bigger. Drugs exhibited restricted penetration and distribution gradients, accumulating preferentially in cells in the outer layers of MCTSs relative to those in the inner cores. Cal33 monolayers were 6-, 20-, 10-, and 16-fold more sensitive than MCTSs to growth inhibition by ellipticine, idarubicin, daunorubicin, and doxorubicin, respectively. In Cal33 MCTSs exposed to ellipticine or doxorubicin for 24 h, MCTSs were smaller and although they still exhibited drug penetration and distribution gradients, the fluorescent intensity difference between outer and inner cells was reduced. After a 24 h exposure, both drugs had penetrated throughout FaDu MCTSs, consistent with drug-induced death of peripheral cell layers enhancing drug penetration. The increased resistance of MCTS cultures and their ability to recapitulate drug penetration and distribution gradients argues strongly for the deployment of these more physiological models in cancer lead discovery. MCTSs have the potential to enhance the correlation between in vitro potencies and in vivo efficacy, and ultimately may lead to improved cancer drug approval rates.

Dataset Information

Macromolecular crowding effect on cartilaginous matrix production: a comparison of two-dimensional and three-dimensional models.

Publications

Macromolecular crowding effect on cartilaginous matrix production: a comparison of two-dimensional and three-dimensional models.

Similar Datasets

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