Neural conversion of ES cells by an inductive activity on human amniotic membrane matrix

doi:10.1073/pnas.0600104103

Neural conversion of ES cells by an inductive activity on human amniotic membrane matrix

*Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;
^†Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;
^§Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan; and
^¶Department of Molecular and System Neurobiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan

Edited by Igor B. Dawid, National Institutes of Health, Bethesda, MD, and approved May 1, 2006 (received for review January 6, 2006)

Abstract

Here we report a human-derived material with potent inductive activity that selectively converts ES cells into neural tissues. Both mouse and human ES cells efficiently differentiate into neural precursors when cultured on the matrix components of the human amniotic membrane in serum-free medium [amniotic membrane matrix-based ES cell differentiation (AMED)]. AMED-induced neural tissues have regional characteristics (brainstem) similar to those induced by coculture with mouse PA6 stromal cells [a common method called stromal cell-derived inducing activity (SDIA) culture]. Like the SDIA culture, the AMED system is applicable to the in vitro generation of various CNS tissues, including dopaminergic neurons, motor neurons, and retinal pigment epithelium. In contrast to the SDIA method, which uses animal cells, the AMED culture uses a noncellular inductive material derived from an easily available human tissue; therefore, AMED should provide a more suitable and versatile system for generating a variety of neural tissues for clinical applications.

Footnotes

^‖To whom correspondence should be addressed at:
Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo, Kobe 650-0047, Japan.
E-mail: sasaicdb{at}mub.biglobe.ne.jp
↵ ^‡Present address: Department of Ophthalmology, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.
Author contributions: M.U., S.K., and Y.S. designed research; M.U., M.M., K.W., T.N., F.O., M.T., and H.K. performed research; M.U. analyzed data; and Y.S. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

Abbreviations:

mES,

mouse ES;

hES,

human ES;

hAM,

human amniotic membrane;

KSR,

knockout serum replacement;

AMED,

amniotic membrane matrix-based ES cell differentiation;

SDIA,

stromal cell-derived inducing activity;

TH,

tyrosine hydroxylase;

Shh,

Sonic hedgehog;

BMP4,

bone morphogenetic protein 4;

RA,

retinoic acid;

EB,

embryoid bodies.