Regulated GDNF Delivery in Vivo Using Neural Stem Cells

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 Parkinson's 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.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2006
Accession Number
ADA455280

Entities

People

  • Clive Svendsen

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Anti-Bacterial Agents
  • Brain
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Chromosomes
  • Diseases And Disorders
  • Environment
  • Growth Factors
  • Neurodegeneration
  • Parkinson'S Disease
  • Peptide Growth Factors
  • Peptides
  • Proteins
  • Stem Cells

Fields of Study

  • Biology

Readers

  • Neuroscience

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech