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Exp Neurol. 2006 May;199(1):143-55. Epub 2006 Feb 7.

A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke.

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1
ReNeuron Ltd., 10 Nugent Road, Surrey Research Park, Guildford, Surrey GU2 7AF, UK.

Abstract

Transplantation of neural stem cells into the brain is a novel approach to the treatment of chronic stroke disability. For clinical application, safety and efficacy of defined, stable cell lines produced under GMP conditions are required. To this end, a human neural stem cell line, CTX0E03, was derived from human somatic stem cells following genetic modification with a conditional immortalizing gene, c-mycER(TAM). This transgene generates a fusion protein that stimulates cell proliferation in the presence of a synthetic drug 4-hydroxy-tamoxifen (4-OHT). The cell line is clonal, expands rapidly in culture (doubling time 50-60 h) and has a normal human karyotype (46 XY). In the absence of growth factors and 4-OHT, the cells undergo growth arrest and differentiate into neurons and astrocytes. Transplantation of CTX0E03 in a rat model of stroke (MCAo) caused statistically significant improvements in both sensorimotor function and gross motor asymmetry at 6-12 weeks post-grafting. In addition, cell migration and long-term survival in vivo were not associated with significant cell proliferation. These data indicate that CTX0E03 has the appropriate biological and manufacturing characteristics necessary for development as a therapeutic cell line.

PMID:
16464451
DOI:
10.1016/j.expneurol.2005.12.011
[Indexed for MEDLINE]
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