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

K Pollock, P Stroemer, S Patel, L Stevanato, A Hope, E Miljan, Z Dong, H Hodges, J Price, J D Sinden

Research output: Contribution to journalArticlepeer-review

240 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)143 - 155
Number of pages13
JournalExperimental Neurology
Volume199
Issue number1
DOIs
Publication statusPublished - May 2006

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