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First published online November 21, 2007
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2007-0588v1
26/2/440    most recent
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Submitted on July 23, 2007
Accepted on November 13, 2007

EMBRYONIC STEM CELLS

A Pure Population of Ectodermal Cells Derived from Human Embryonic Stem Cells

Edith Aberdam 1, Efrat Barak 2, Matthieu Rouleau 3, Stephanie De Laforest 3, Sonia Berrih-aknin 4, David M. Suter 5, Karl Heinz Krause 5, Michal Amit 6, Joseph Itskovitz-Eldor 7, Daniel Aberdam 1*

1 INSERM, U898, Nice F-06107, France, Université de Nice-Sophia Antipolis, Nice F-06107, France, INSERTECH, Bruce Rappaport Institute, Technion, 31096 Haifa, Israel
2 INSERTECH, Bruce Rappaport Institute, Technion, 31096 Haifa, Israel
3 INSERM, U898, Nice F-06107, France, Université de Nice-Sophia Antipolis, Nice F-06107, France
4 INSERTECH, Bruce Rappaport Institute, Technion, 31096 Haifa, Israel, UMR CNRS 8162, Université Paris XI, Hôpital Marie Lannelongue, Le Plessis-Robinson, France
5 Foundation for Medical Research, University of Geneva, Geneva, Switzerland
6 Stem Cell Center, Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, Israel
7 INSERTECH, Bruce Rappaport Institute, Technion, 31096 Haifa, Israel, Stem Cell Center, Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, Israel, Department of Ob-Gyn, Rambam Health Care Campus, 31096 Haifa, Israel.

* To whom correspondence should be addressed. E-mail: aberdam{at}unice.fr.


   Abstract

Embryonic stem (ES) cells represent a unique cellular model to recapitulate in vitro early steps of embryonic development, and an unlimited cellular source in therapy for many diseases as well as targets for drug discovery and toxicology screens. Although previous studies have reported epidermal differentiation of mouse and human ES (huES) cells, the heterogeneity of the resulting cell culture impairs the evaluation of differentiated cells for cell therapy. We report here the reproducible isolation of a homogenous ectodermal cell population IT1 from human ES cells. Like primary cells, IT1 remains homogenous over 15 passages, expands up to 60 population doublings and then dies through senescence. Accordingly, IT1 displays a normal karyotype, a somatic cell cycle kinetics and does not produce teratoma in nude mice. The production of K14-expressing epithelial cells driven by p63 expression strengthens the ectodermal nature of IT1 cells. Since IT1 can be isolated from different huES cell lines, it may provide a ready source of ectodermal progenitors for the development of toxicology cell model, new-drug-screening strategies and cell therapy transplantation.

______________________________________________________________________________

E. Aberdam and E. Barak contributed equally to this work.

Key Words. embryonic stem cells, ES, ectodermal cells, p63, K14, K18







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