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  Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors

Stachelscheid, H., Wulf-Goldenberg, A., Eckert, K., Jensen, J., Edsbagge, J., Bjorquist, P., et al. (2012). Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors. Journal of Tissue Engineering and Regenerative Medicine, 2012, e-e. doi:10.1002/term.1467.

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© 2012 John Wiley & Sons, Inc
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Stachelscheid, H., Author
Wulf-Goldenberg, A., Author
Eckert, K., Author
Jensen, J., Author
Edsbagge, J., Author
Bjorquist, P., Author
Rivero, M., Author
Strehl, R., Author
Jozefczuk, J.1, Author           
Prigione, A.1, Author           
Adjaye, J.1, Author           
Urbaniak, T., Author
Bussmann, P., Author
Zeilinger, K., Author
Gerlach, J. C., Author
Affiliations:
1Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479654              

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Free keywords: human embryonic stem cells; bioreactor; in vitro model; 3D tissue formation; differentiation; teratoma; embryoid body
 Abstract: Teratoma formation in mice is today the most stringent test for pluripotency that is available for human pluripotent cells, as chimera formation and tetraploid complementation cannot be performed with human cells. The teratoma assay could also be applied for assessing the safety of human pluripotent cell-derived cell populations intended for therapeutic applications. In our study we examined the spontaneous differentiation behaviour of human embryonic stem cells (hESCs) in a perfused 3D multi-compartment bioreactor system and compared it with differentiation of hESCs and human induced pluripotent cells (hiPSCs) cultured in vitro as embryoid bodies and in vivo in an experimental mouse model of teratoma formation. Results from biochemical, histological/immunohistological and ultrastuctural analyses revealed that hESCs cultured in bioreactors formed tissue-like structures containing derivatives of all three germ layers. Comparison with embryoid bodies and the teratomas revealed a high degree of similarity of the tissues formed in the bioreactor to these in the teratomas at the histological as well as transcriptional level, as detected by comparative whole-genome RNA expression profiling. The 3D culture system represents a novel in vitro model that permits stable long-term cultivation, spontaneous multi-lineage differentiation and tissue formation of pluripotent cells that is comparable to in vivo differentiation. Such a model is of interest, e.g. for the development of novel cell differentiation strategies. In addition, the 3D in vitro model could be used for teratoma studies and pluripotency assays in a fully defined, controlled environment, alternatively to in vivo mouse models. Copyright (c) 2012 John Wiley & Sons, Ltd.

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Language(s): eng - English
 Dates: 2012-03-21
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/term.1467
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Title: Journal of Tissue Engineering and Regenerative Medicine
Source Genre: Journal
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Publ. Info: John Wiley & Sons, Inc.
Pages: - Volume / Issue: 2012 Sequence Number: - Start / End Page: e - e Identifier: -