Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNF-producing cells in a rat model of Parkinson's disease.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to possess potent neurotrophic effects on dopaminergic (DA) neurons. We attempted the transplantation of encapsulated GDNF-producing cells to generate a stable supply of GDNF in the brain to promote neuroprotective and restorative effects for DA neurons. We established baby hamster kidney (BHK) cells and introduced GDNF cDNA to produce human GDNF (BHK-GDNF). These BHK-GDNF cells, or nontransfected BHK cells (BHK-Control), were encapsulated into hollow fibers, and the polymer encapsulated cells were unilaterally implanted into the striatum of adult rats, either before or after the administration of 6-hydroxydopamine into the same striatum. The encapsulated BHK-GDNF cells produced GDNF continuously in the striatum for up to 6 months. The rats that received a BHK-GDNF capsule showed a significant decrease in rotational behaviour compared to those that received a BHK-control capsule. Preservation of the nigrostriatal pathway was significantly greater in those that received a BHK-GDNF capsule than in those that received a BHK-control capsule. This indicates that encapsulated GDNF-producing cells can supply GDNF in a stable fashion and have protective and restorative effects on host DA neurons. Our results support a role for this grafting technique in the treatment of Parkinson's disease.
Shingo
Tetsuro
T
Department of Neurological Surgery, Okayama University Medical School, Japan. teshingo@aol.com
Date
Isao
I
Yoshida
Hideyuki
H
Ohmoto
Takashi
T
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D002214:Capsules; D002460:Cell Line / Q000378:metabolism / Q000637:transplantation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D003337:Corpus Callosum / Q000166:cytology; D003342:Corpus Striatum / Q000166:cytology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival; D006801:Humans; D007668:Kidney / Q000166:cytology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D020734:Parkinsonian Disorders / Q000601:surgery*; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; 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; D009419:Nerve Tissue Proteins; D011108:Polymers; D014446:Tyrosine 3-Monooxygenase