Faculty Collaboration Database

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates. Gene Ther 2006 Mar;13(5):379-88

Date

12/16/2005

Pubmed ID

16355116

DOI

10.1038/sj.gt.3302679

Scopus ID

2-s2.0-33645140627 (requires institutional sign-in at Scopus site)   151 Citations

Abstract

Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.

Author List

Behrstock S, Ebert A, McHugh J, Vosberg S, Moore J, Schneider B, Capowski E, Hei D, Kordower J, Aebischer P, Svendsen CN

Author

Allison D. Ebert PhD Center Director, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Brain
Dopamine
Genetic Therapy
Genetic Vectors
Glial Cell Line-Derived Neurotrophic Factor
Haplorhini
Humans
Immunohistochemistry
Lentivirus
Neurons
Parkinsonian Disorders
Rats
Rats, Sprague-Dawley
Stem Cell Transplantation
Stem Cells
Transduction, Genetic