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

Moschidou, Dafni, Mukherjee, Sayandip, Blundell, Michael P., Drews, Katharina, Jones, Gemma N., Abdulrazzak, Hassan, Nowakowska, Beata, Phoolchund, Anju, Lay, Kenneth, Tamasamy, T. Selvee, Cananzi, Mara, Nettersheim, Daniel, Sullivan, Mark, Frost, Jennifer, Moore, Gudrun, Vermeesch, Joris R., Fisk, Nicholas M., Thrasher, Adrian J., Atala, Anthony, Adjaye, James, Schorle, Hubert, De Coppi, Paolo and Guillot, Pascale V. (2012) Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach. Molecular Therapy, 20 10: 1953-1967.


Author Moschidou, Dafni
Mukherjee, Sayandip
Blundell, Michael P.
Drews, Katharina
Jones, Gemma N.
Abdulrazzak, Hassan
Nowakowska, Beata
Phoolchund, Anju
Lay, Kenneth
Tamasamy, T. Selvee
Cananzi, Mara
Nettersheim, Daniel
Sullivan, Mark
Frost, Jennifer
Moore, Gudrun
Vermeesch, Joris R.
Fisk, Nicholas M.
Thrasher, Adrian J.
Atala, Anthony
Adjaye, James
Schorle, Hubert
De Coppi, Paolo
Guillot, Pascale V.
Title Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach
Journal name Molecular Therapy   Check publisher's open access policy
ISSN 1525-0016
1525-0024
Publication date 2012-07
Sub-type Article (original research)
DOI 10.1038/mt.2012.117
Volume 20
Issue 10
Start page 1953
End page 1967
Total pages 15
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2013
Language eng
Formatted abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 3 July 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
 
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Created: Tue, 29 May 2012, 11:47:59 EST by Professor Nicholas Fisk on behalf of UQ Centre for Clinical Research