{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:15:25Z","timestamp":1790201725697,"version":"4.1.0"},"reference-count":27,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T00:00:00Z","timestamp":1349827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:p>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\u201360, and TRA-1\u201381, 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\u201360, and TRA-1\u201381. Supplementation with VPA for 5 days further upregulated OCT4, KLF4, and SOX2, and induced expression of NANOG, SSEA3, TRA-1\u201360, and TRA-1\u201381, 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.<\/jats:p>","DOI":"10.1089\/scd.2012.0267","type":"journal-article","created":{"date-parts":[[2012,10,11]],"date-time":"2012-10-11T07:49:45Z","timestamp":1349941785000},"page":"444-458","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":58,"title":["Human Mid-Trimester Amniotic Fluid Stem Cells Cultured Under Embryonic Stem Cell Conditions with Valproic Acid Acquire Pluripotent Characteristics"],"prefix":"10.1177","volume":"22","author":[{"given":"Dafni","family":"Moschidou","sequence":"first","affiliation":[{"name":"Imperial College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayandip","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Blundell","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma N.","family":"Jones","sequence":"additional","affiliation":[{"name":"Imperial College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Atala","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Fisk","sequence":"additional","affiliation":[{"name":"University of Queensland","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"De Coppi","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale V.","family":"Guillot","sequence":"additional","affiliation":[{"name":"Imperial College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,10,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2001.27945"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1291"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1072-7515(02)01834-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deg279"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh279"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7310043"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1274"},{"key":"e_1_3_3_9_2","first-page":"987","article-title":"Activation of ectopic Oct-4 and Rex-1 promoters in human amniotic fluid cells","volume":"16","author":"Karlmark KR","year":"2005","unstructured":"Karlmark KR, , Freilinger A, , Marton E, , Rosner M, , Lubec G, , Hengstschl\u00e4ger M. 2005. 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