Human mid-trimester amniotic fluid stem cells cultured under embryonic stem cell conditions with valproic acid acquire pluripotent characteristics

Moschidou, Dafni, Mukherjee, Sayandip, Blundell, Michael P., Jones, Gemma N., Atala, Anthony J., Thrasher, Adrian J., Fisk, Nicholas M., De Coppi, Paolo and Guillot, Pascale V. (2013) Human mid-trimester amniotic fluid stem cells cultured under embryonic stem cell conditions with valproic acid acquire pluripotent characteristics. Stem Cells and Development, 22 3: 444-458. doi:10.1089/scd.2012.0267


Author Moschidou, Dafni
Mukherjee, Sayandip
Blundell, Michael P.
Jones, Gemma N.
Atala, Anthony J.
Thrasher, Adrian J.
Fisk, Nicholas M.
De Coppi, Paolo
Guillot, Pascale V.
Title Human mid-trimester amniotic fluid stem cells cultured under embryonic stem cell conditions with valproic acid acquire pluripotent characteristics
Journal name Stem Cells and Development   Check publisher's open access policy
ISSN 1547-3287
1557-8534
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1089/scd.2012.0267
Volume 22
Issue 3
Start page 444
End page 458
Total pages 15
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Collection year 2013
Language eng
Abstract Human mid-trimester amniotic fluid stem cells (AFSC) have promising applications in regenerative medicine, being broadly multipotent with an intermediate phenotype between embryonic (ES) and mesenchymal stem cells (MSC). Despite this propluripotent phenotype, AFSC are usually cultured in adherence in a serum-based expansion medium, and how expansion in conditions sustaining pluripotency might affect their phenotype remains unknown. We recently showed that early AFSC from first trimester amniotic fluid, which endogenously express Sox2 and Klf4, can be reprogrammed to pluripotency without viral vectors using the histone deacetylase inhibitor valproic acid (VPA). Here, we show that mid-trimester AFSC cultured under MSC conditions contained a subset of cells endogenously expressing telomerase, CD24, OCT4, C-MYC, and SSEA4, but low/null levels of SOX2, NANOG, KLF4, SSEA3, TRA-1–60, and TRA-1–81, with cells unable to form embryoid bodies (EBs) or teratomas. In contrast, AFSC cultured under human ESC conditions were smaller in size, grew faster, formed colonies, upregulated OCT4 and C-MYC, and expressed KLF4 and SOX2, but not NANOG, SSEA3, TRA-1–60, and TRA-1–81. Supplementation with VPA for 5 days further upregulated OCT4, KLF4, and SOX2, and induced expression of NANOG, SSEA3, TRA-1–60, and TRA-1–81, with cells now able to form EBs and teratomas. We conclude that human mid-trimester AFSC, which may be isolated autologously during pregnancy without ethics restriction, can acquire pluripotent characteristics without the use of ectopic factors. Our data suggest that this medium-dependant approach to pluripotent mid-trimester AFSC reflects true reprogramming and not the selection of prepluripotent cells.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Online Ahead of Print: November 27, 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
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