Increased fiber outgrowth from xeno-transplanted human embryonic dopaminergic neurons with co-implants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor

We investigated whether a continuous supply of glial cell line-derived neurotrophic factor (GDNF) via encapsulated genetically modified cells can promote survival and fiber outgrowth from xenotransplanted human dopaminergic neurons. Cells genetically engineered to continuously secrete GDNF were conf...

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Bibliographic Details
Published in:Brain research bulletin 2005-07, Vol.66 (2), p.135-142
Main Authors: Ahn, Young-Hwan, Bensadoun, Jean-Charles, Aebischer, Patrick, Zurn, Anne D., Seiger, Åke, Björklund, Anders, Lindvall, Olle, Wahlberg, Lars, Brundin, Patrik, Kaminski Schierle, Gabriele S.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Basic Medicine
Behavior, Animal - drug effects
Behavior, Animal - physiology
Capsules
Cell Size - drug effects
Dopamine
Dopamine - metabolism
Embryo, Mammalian
Female
Fetal Tissue Transplantation - methods
Functional Laterality
GDNF
Genetic Engineering - methods
Glial Cell Line-Derived Neurotrophic Factor
Humans
Immunohistochemistry - methods
Implants, Experimental
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Mesencephalon - cytology
Motor Activity - drug effects
Nerve Fibers - drug effects
Nerve Fibers - physiology
Nerve Growth Factors - biosynthesis
Nerve Growth Factors - pharmacology
Neuroglia - physiology
Neurons - physiology
Neurosciences
Neurotrophic factor
Neurovetenskaper
Oxidopamine - toxicity
Polymer
Rats
Rats, Sprague-Dawley
Rotarod Performance Test - methods
Time Factors
Tyrosine 3-Monooxygenase - metabolism
Xenotransplantation
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Summary:We investigated whether a continuous supply of glial cell line-derived neurotrophic factor (GDNF) via encapsulated genetically modified cells can promote survival and fiber outgrowth from xenotransplanted human dopaminergic neurons. Cells genetically engineered to continuously secrete GDNF were confined in hollow fiber-based macrocapsules. Each hemiparkinsonian rat received either a single C2C12-hGDNF capsule ( n = 8) or a C2C12-control capsule ( n = 8) concomitantly with human embryonic ventral mesencephalic cell suspension transplants. Our results show that fiber outgrowth in the area between the capsule and the graft is more extensive in rats with GDNF-releasing capsules than in rats with control capsules. We suggest that continuous and safe delivery of GDNF to the brain could be a potential way to optimize neural transplantation as a therapy for Parkinson's disease.
ISSN:0361-9230
1873-2747
DOI:10.1016/j.brainresbull.2005.04.009