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  Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach

Moschidou, D., Mukherjee, S., Blundell, M. P., Drews, K., Jones, G. N., Abdulrazzak, H., et al. (2012). Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach. Molecular Therapy, 20(10), 1953-1967. doi:10.1038/mt.2012.117.

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Datensatz-Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F078-E Versions-Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F079-C
Genre: Zeitschriftenartikel

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© 2012 American Society of Gene & Cell Therapy
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 Urheber:
Moschidou, D., Autor
Mukherjee, S., Autor
Blundell, M. P., Autor
Drews, K.1, Autor              
Jones, G. N., Autor
Abdulrazzak, H., Autor
Nowakowska, B., Autor
Phoolchund, A., Autor
Lay, K., Autor
Ramasamy, T. S., Autor
Cananzi, M., Autor
Nettersheim, D., Autor
Sullivan, M., Autor
Frost, J., Autor
Moore, G., Autor
Vermeesch, J. R., Autor
Fisk, N. M., Autor
Thrasher, A. J., Autor
Atala, A., Autor
Adjaye, J.1, Autor              
Schorle, H., AutorDe Coppi, P., AutorGuillot, P. V., Autor mehr..
Affiliations:
1Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1479654              

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 Zusammenfassung: Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success. Here, we show that c-KIT+ human first-trimester amniotic fluid stem cells (AFSCs) can be fully reprogrammed to pluripotency without ectopic factors, by culture on Matrigel in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo. After long-term expansion, they maintain genetic stability, protein level expression of key pluripotency factors, high cell-division kinetics, telomerase activity, repression of X-inactivation, and capacity to differentiate into lineages of the three germ layers, such as definitive endoderm, hepatocytes, bone, fat, cartilage, neurons, and oligodendrocytes. We conclude that AFSC can be utilized for cell banking of patient-specific pluripotent cells for potential applications in allogeneic cellular replacement therapies, pharmaceutical screening, and disease modeling.

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 Datum: 2012-07-032012-10
 Publikationsstatus: Im Druck publiziert
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/mt.2012.117
 Art des Abschluß: -

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Titel: Molecular Therapy
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Nature Publishing Group
Seiten: - Band / Heft: 20 (10) Artikelnummer: - Start- / Endseite: 1953 - 1967 Identifikator: ISSN: 1525-0016
CoNE: http://pubman.mpdl.mpg.de/cone/journals/resource/961066780010