Developing Human Embryonic Stem Cells for Grafting in Parkinson's Disease
Annual rept. 1 Mar 2004-28 Feb 2005
LUND UNIV (SWEDEN)
Pagination or Media Count:
The project aims to differentiate human embryonic stem cells hESCs into dopaminergic neurons for use in neural grafting in Parkinsons disease PD. During the first year we studied the survival and differentiation potential of hESCs implanted into a rat model of PD. hESCs were differentiated on PA6 feeders for 16, 20 and 23 days prior to grafting. The number of neurons and dopaminergic cells increased with time in vitro. 100,000 viable cells were grafted into the striatum of immunosuppressed 6-OHDA-lesioned rats. The grafted hESCs-derived cells survived well in all groups. Substantial number of surviving cells differentiated into neurons NeuN positive but very few hESC-derived TH positive neurons were observed in most transplanted rats. Amphetamine-induced rotational behavior was tested at weeks 2, 4, 8 and 13 after transplantation. No behavioral recovery was observed. Importantly, the rats grafted with hESCs differentiated for 16 days developed severe teratomas staring from 6 weeks post-transplantation, while most rats grafted with hESCs differentiated in vitro for longer periods kept healthy until the end of the experiment. This indicates that differentiated hESCs can survive and retain neuronal phenotype after transplantation despite low numbers of dopaminergic neurons and that the differentiation of pre-transplantation is essential to prevent teratoma-formation.
- Anatomy and Physiology
- Medicine and Medical Research