Functional engraftment of human ES cell–derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-11

AUTHORS

Neeta S Roy, Carine Cleren, Shashi K Singh, Lichuan Yang, M Flint Beal, Steven A Goldman

ABSTRACT

To direct human embryonic stem (HES) cells to a dopaminergic neuronal fate, we cocultured HES cells that were exposed to both sonic hedgehog and fibroblast growth factor 8 with telomerase-immortalized human fetal midbrain astrocytes. These astrocytes substantially potentiated dopaminergic neurogenesis by both WA09 and WA01 HES cells, biasing them to the A9 nigrostriatal phenotype. When transplanted into the neostriata of 6-hydroxydopamine-lesioned parkinsonian rats, the dopaminergic implants yielded a significant, substantial and long-lasting restitution of motor function. However, although rich in donor-derived tyrosine hydroxylase-expressing neurons, the grafts exhibited expanding cores of undifferentiated mitotic neuroepithelial cells, which can be tumorigenic. These results show the utility of recreating the cellular environment of the developing human midbrain while driving dopaminergic neurogenesis from HES cells, and they demonstrate the potential of the resultant cells to mediate substantial functional recovery in a model of Parkinson disease. Yet these data also mandate caution in the clinical application of HES cell-derived grafts, given their potential for phenotypic instability and undifferentiated expansion. More... »

PAGES

1259-1268

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm1495

DOI

http://dx.doi.org/10.1038/nm1495

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034580186

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17057709


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