Regulated GDNF Delivery in Vivo Using Neural Stem Cells
Abstract
The major aim of this proposal was to establish lines of neural stem cells secreting GDNF under a regulatable promoter system which may be used for future transplant therapies for PD. The tasks of the first year have been met. We have changed from using rodent and monkey stem cells to using human stem cells (hNSC) due to better growth and infection profiles for human cells. We have shown that hNSC can be infected with lenti-GDNF. GDNF released from the cells is functional on dopamine neurons and can be switched on and off by doxycycline. We have enhanced infection rates such that over 85% of cells express GDNF. We have selected high expressing lines and shown that they can be expanded in culture for over 20 weeks without losing the ability to produce GDNF in a regulated fashion. We have performed 6-OHDA lesions in rats to induce PD and shown loss of TH expression, survival of hNSC transplanted into these animals and expression of GDNF for up to 8 weeks (this is ahead of our predicted time frame) but are currently starting in vivo regulation studies. PET analysis has shown that the lesion can be detected with imaging and we are currently optimizing this protocol for use in the more detailed studies next year. Our pilot monkey work has been delayed due to problems growing the monkey stem cells. However, we have now scheduled the first surgery using hNSC for May 2004.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA428919
Entities
People
- Clive N. Svendsen
Organizations
- University of Wisconsin–Madison