Stem Cells
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First published online November 16, 2006
Stem Cells Vol. 25 No. 3 March 2007, pp. 562 -570
doi:10.1634/stemcells.2006-0011; www.StemCells.com
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EMBRYONIC STEM CELLS: CHARACTERIZATION SERIES

Electrical Stimulation Modulates Fate Determination of Differentiating Embryonic Stem Cells

Masahisa Yamadaa,b, Kentaro Tanemurac,d, Seiji Okadaf, Akio Iwanamif, Masaya Nakamurag, Hideaki Mizunoe, Michiru Ozawac, Ritsuko Ohyama-Gotoc, Naohito Kitamurab, Masako Kawanoa, Kyoko Tan-Takeuchia, Chiho Ohtsukac, Atsushi Miyawakie, Akihiko Takashimad, Masaharu Ogawaa, Yoshiaki Toyamag, Hideyuki Okanof, Takashi Kondoc

aLaboratory for Cell Culture Development,
bYamada Research Unit, Molecular Neuropathology Group;
cKondo Research Unit, Brain Development Research Group;
dLaboratory for Alzheimer's Disease;
eLaboratory for Cell Function Dynamics, Brain Science Institute, Institute of Physical and Chemical Research, Saitama, Japan;
fDepartment of Physiology and
gDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan

Key Words. Calcium flux • Tissue regeneration • Neuron • Embryonic stem cells

Correspondence: Takashi Kondo, Ph.D., BSI, RIKEN, Brain Development Research Group, 2-1 Hirosawa Wako Saitama 351-0198 Japan. Telephone: +81 48-467-6729; Fax: +81 48-467-6729; e-mail: tkondo{at}brain.riken.jp

Received January 5, 2006; accepted for publication November 8, 2006.
First published online in STEM CELLS EXPRESS   November 16, 2006.



A clear understanding of cell fate regulation during differentiation is key in successfully using stem cells for therapeutic applications. Here, we report that mild electrical stimulation strongly influences embryonic stem cells to assume a neuronal fate. Although the resulting neuronal cells showed no sign of specific terminal differentiation in culture, they showed potential to differentiate into various types of neurons in vivo, and, in adult mice, contributed to the injured spinal cord as neuronal cells. Induction of calcium ion influx is significant in this differentiation system. This phenomenon opens up possibilities for understanding novel mechanisms underlying cellular differentiation and early development, and, perhaps more importantly, suggests possibilities for treatments in medical contexts.




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