title: Amniotic fluid cells are more efficiently reprogrammed to pluripotency than adult cells.
abstract: Recently, cultured human adult skin cells were reprogrammed to induced pluripotent stem (iPS) cells, which have characteristics similar to human embryonic stem (hES) cells. Patient-derived iPS cells offer genetic and immunologic advantages for cell and tissue replacement or engineering. The efficiency of generating human iPS cells has been very low; therefore an easily and efficiently reprogrammed cell type is highly desired. Here, we demonstrate that terminally differentiated human amniotic fluid (AF) skin cells provide an accessible source for efficiently generating abundant-induced pluripotent stem (AF-iPS) cells. By induction of pluripotency with the transcription factor quartet (OCT3/4, SOX2, KLF4, and c-MYC) the terminally differentiated, cultured AF skin cells formed iPS colonies approximately twice as fast and yielded nearly a two-hundred percent increase in number, compared to cultured adult skin cells. AF-iPS cells were identical to hES cells for morphological and growth characteristics, antigenic stem cell markers, stem cell gene expression, telomerase activity, in vitro and in vivo differentiation into the three germ layers and for their capacity to form embryoid bodies (EBs) and teratomas. Our findings provide a biological interesting conclusion that these fetal AF cells are more rapidly, easily, and efficiently reprogrammed to pluripotency than neonatal and adult cells. AF-iPS cells may have a "young," more embryonic like epigenetic background, which may facilitate and accelerate pluripotency. The ability to efficiently and rapidly reprogram terminally differentiated AF skin cells and generate induced pluripotent stem cells provides an abundant iPS cell source for various basic studies and a potential for future patient-specific personalized therapies.
authors.affiliation: Department of Medicine, Cardiovascular Research Center, Mount Sinai School of Medicine , New York, NY 10029, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Galende
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karakikes
authors.forename: Lisa
authors.initials: L
authors.lastname: Edelmann
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerenyi
authors.forename: Georges
authors.initials: G
authors.lastname: Khoueiry
authors.forename: James
authors.initials: J
authors.lastname: Lafferty
authors.forename: Joseph T
authors.initials: JT
authors.lastname: McGinn
authors.forename: Michael
authors.initials: M
authors.lastname: Brodman
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Katalin
authors.initials: K
authors.lastname: Polgar
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D044127:Epigenesis, Genetic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007231:Infant, Newborn; D000090062:Kruppel-Like Factor 4; D051379:Mice; D016513:Mice, SCID; D019098:Telomerase / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D019098:Telomerase