Open AccessDirected Differentiation and Transplantation of Human Embryonic Stem Cell‐Derived Motoneurons
Author(s) -
Lee Hyojin,
Shamy George Al,
Elkabetz Yechiel,
Schofield Claude M.,
Harrsion Neil L.,
Panagiotakos Georgia,
Socci Nicholas D.,
Tabar Viviane,
Studer Lorenz
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0097
Subject(s) - biology , embryonic stem cell , spinal muscular atrophy , sonic hedgehog , choline acetyltransferase , transplantation , motor neuron , stem cell , neural stem cell , cellular differentiation , neuroscience , microbiology and biotechnology , spinal cord , central nervous system , genetics , medicine , signal transduction , gene
Motoneurons represent a specialized class of neurons essential for the control of body movement. Motoneuron loss is the cause of a wide range of neurological disorders including amyotrophic lateral sclerosis and spinal muscular atrophy. Embryonic stem cells are a promising cell source for the study and potential treatment of motoneuron diseases. Here, we present a novel in vitro protocol of the directed differentiation of human embryonic stem cells (hESCs) into engraftable motoneurons. Neural induction of hESCs was induced on MS5 stromal feeders, resulting in the formation of neural rosettes. In response to sonic hedgehog and retinoic acid, neural rosettes were efficiently directed into spinal motoneurons with appropriate in vitro morphological, physiological, and biochemical properties. Global gene expression analysis was used as an unbiased measure to confirm motoneuron identity and type. Transplantation of motoneuron progeny into the developing chick embryo resulted in robust engraftment, maintenance of motoneuron phenotype, and long‐distance axonal projections into peripheral host tissues. Transplantation into the adult rat spinal cord yielded neural grafts comprising a large number of human motoneurons with outgrowth of choline acetyltransferase positive fibers. These data provide evidence for in vivo survival of hESC‐derived motoneurons, a key requirement in the development of hESC‐based cell therapy in motoneuron disease. Disclosure of potential conflicts of interest is found at the end of this article.