Accession Number:

ADA455280

Title:

Regulated GDNF Delivery in Vivo Using Neural Stem Cells

Descriptive Note:

Annual rept. 1 Apr 2005-31 Mar 2006

Corporate Author:

WISCONSIN UNIV-MADISON

Personal Author(s):

• Svendsen, Clive

Report Date:

2006-04-01

Pagination or Media Count:

26.0

Abstract:

This year we have published a major paper describing how hNPC-GDNF can survive and integrate into the damaged rodent brain and release GDNF for long periods. This GDNF was sufficient to induce up regulation or sprouting of dopamine neurons. We have also established that the lesion environment is crucial for both the migration and survival of transplanted cells. In our regulation studies it is clear that the single vector tTRK system, while very efficient in vitro does not work well in vivo - possibly due to low expression levels with this construct. We have begun working with a new construct which may overcome this problem. Our imaging studies have shown that rats have terminal lesions which remain consistent over time. Finally we have shown that hNPC-GDNF can also survive in the MPTP treated Parkinsonian monkey and release GDNF which increases TH activity within targeted regions of the striatum. This is an important first step showing that this technology is able to deliver GDNF in the best model of Parkinsons disease we currently have. Afurther 15 animals are currently being transplanted with cells generated within the current grant. We plan to perform some imaging studies on these animals in the final year.

Descriptors:

• *STEM CELLS
• DELIVERY
• ENVIRONMENTS
• DAMAGE
• BRAIN
• RATS
• EFFICIENCY
• LONG RANGE(TIME)
• SURVIVAL(GENERAL)
• IN VITRO ANALYSIS
• CONSISTENCY
• IMAGES
• LOW LEVEL
• NERVOUS SYSTEM
• NERVE CELLS
• ANIMALS
• RODENTS
• IN VIVO ANALYSIS
• PARKINSONS DISEASE
• CELLS(BIOLOGY)
• DOPAMINE
• LESIONS
• SURGICAL TRANSPLANTATION

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE