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Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells

Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells
Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells
Embryonic stem cells (ESCs) are pluripotent and have the ability to differentiate into mineralising cells in vitro. The use of pluripotent cells in engineered bone substitutes will benefit from the development of bioactive scaffolds which encourage cell differentiation and tissue development. Extracellular matrix (ECM) may be a suitable candidate for use in such scaffolds since it plays an active role in cellular differentiation. Here, we test the hypothesis that tissue-specific ECM influences the differentiation of murine ESCs. We induced murine ESCs to differentiate by embryoid body formation, followed by dissociation and culture on ECM prepared by decellularisation of either osteogenic cell (MC3T3-E1) or non-osteogenic cell (A549) cultures, or on defined collagen type I matrix. We assessed osteogenic differentiation by formation of mineralised tissue and osteogenic gene expression, and found it to be significantly greater on MC3T3-E1 matrices than on any other matrix. The osteogenic effect of MC3T3-E1 matrix was reduced by heat treatment and abolished by trypsin, suggesting a bioactive proteinaceous component. These results demonstrate that decellularised bone-specific ECM promotes the osteogenic differentiation of ESCs. Our results are of fundamental interest and may help in tailoring scaffolds for tissue engineering applications which both incorporate tissue-specific ECM signals and stimulate stem-cell differentiation.
embryonic stem cells, extracellular matrix, osteogenic, decellularised matrix, tissue engineering, differentiation
0142-9612
3244-3252
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Gentleman, Eileen
a0b4959e-7b65-46b7-9ea8-1d0f5857c22f
Chen, Xinyong
6d1e3fee-a5ca-4e55-8809-b24f05beb8ca
Roberts, Clive J.
ebc3d2c0-0749-40bd-b371-cdbf022c961b
Polak, Julia M.
fcc91fe8-0c5d-404e-8528-3ca2719ecb77
Stevens, Molly M.
f0c6dded-e31c-4e40-bfc4-2a70fad118a6
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Gentleman, Eileen
a0b4959e-7b65-46b7-9ea8-1d0f5857c22f
Chen, Xinyong
6d1e3fee-a5ca-4e55-8809-b24f05beb8ca
Roberts, Clive J.
ebc3d2c0-0749-40bd-b371-cdbf022c961b
Polak, Julia M.
fcc91fe8-0c5d-404e-8528-3ca2719ecb77
Stevens, Molly M.
f0c6dded-e31c-4e40-bfc4-2a70fad118a6

Evans, Nicholas D., Gentleman, Eileen, Chen, Xinyong, Roberts, Clive J., Polak, Julia M. and Stevens, Molly M. (2010) Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells. Biomaterials, 31 (12), 3244-3252. (doi:10.1016/j.biomaterials.2010.01.039). (PMID:20149448)

Record type: Article

Abstract

Embryonic stem cells (ESCs) are pluripotent and have the ability to differentiate into mineralising cells in vitro. The use of pluripotent cells in engineered bone substitutes will benefit from the development of bioactive scaffolds which encourage cell differentiation and tissue development. Extracellular matrix (ECM) may be a suitable candidate for use in such scaffolds since it plays an active role in cellular differentiation. Here, we test the hypothesis that tissue-specific ECM influences the differentiation of murine ESCs. We induced murine ESCs to differentiate by embryoid body formation, followed by dissociation and culture on ECM prepared by decellularisation of either osteogenic cell (MC3T3-E1) or non-osteogenic cell (A549) cultures, or on defined collagen type I matrix. We assessed osteogenic differentiation by formation of mineralised tissue and osteogenic gene expression, and found it to be significantly greater on MC3T3-E1 matrices than on any other matrix. The osteogenic effect of MC3T3-E1 matrix was reduced by heat treatment and abolished by trypsin, suggesting a bioactive proteinaceous component. These results demonstrate that decellularised bone-specific ECM promotes the osteogenic differentiation of ESCs. Our results are of fundamental interest and may help in tailoring scaffolds for tissue engineering applications which both incorporate tissue-specific ECM signals and stimulate stem-cell differentiation.

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More information

Published date: April 2010
Keywords: embryonic stem cells, extracellular matrix, osteogenic, decellularised matrix, tissue engineering, differentiation

Identifiers

Local EPrints ID: 176179
URI: http://eprints.soton.ac.uk/id/eprint/176179
ISSN: 0142-9612
PURE UUID: f9794563-2256-4e4d-bc85-641bfe87d133
ORCID for Nicholas D. Evans: ORCID iD orcid.org/0000-0002-3255-4388

Catalogue record

Date deposited: 07 Mar 2011 14:08
Last modified: 14 Mar 2024 02:56

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Contributors

Author: Eileen Gentleman
Author: Xinyong Chen
Author: Clive J. Roberts
Author: Julia M. Polak
Author: Molly M. Stevens

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