Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature Medicine 12, 1259 - 1268 (2006)
Published online: 22 October 2006 | doi:10.1038/nm1495
There is a Corrigendum (March 2007) associated with this Article.
Functional engraftment of human ES cell–derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes
Neeta S Roy1, Carine Cleren1, Shashi K Singh1, Lichuan Yang1, M Flint Beal1 & Steven A Goldman1,2
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.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Stem cells: the good, bad and barely in controlNature Medicine News and Views (01 Nov 2006)
Neural stem cells, scaffolds, and chaperonesNature Biotechnology Research News (01 Nov 2002)
See all 3 matches for News And ViewsRESEARCH
Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian miceNature Biotechnology Research (01 Oct 2003)
Conditions for Tumor-free and Dopamine Neuron?enriched Grafts After Transplanting Human ES Cell?derived Neural Precursor CellsMolecular Therapy Original Article
See all 57 matches for Research