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 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.
Ahn
Young-Hwan
YH
Wallenberg Neuroscience Center, Section for Neuronal Survival, BMC A10, SE-221 84 Lund, Sweden. yhahn@ajou.ac.kr
Bensadoun
Jean-Charles
JC
Aebischer
Patrick
P
Zurn
Anne D
AD
Seiger
Ake
A
Björklund
Anders
A
Lindvall
Olle
O
Wahlberg
Lars
L
Brundin
Patrik
P
Kaminski Schierle
Gabriele S
GS
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002214:Capsules; D048429:Cell Size / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods*; D007839:Functional Laterality; D005818:Genetic Engineering / Q000379:methods; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020007:Implants, Experimental; D008636:Mesencephalon / Q000166:cytology; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000494:pharmacology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test / Q000379:methods; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002214:Capsules; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine