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

被引:28
作者
Ahn, YH
Bensadoun, JC
Aebischer, P
Zurn, AD
Seiger, Å
Björklund, A
Lindvall, O
Wahlberg, L
Brundin, P
Schierle, GSK
机构
[1] Sect Neuronal Survival, Wallenberg Neurosci Ctr, SE-22184 Lund, Sweden
[2] Ecole Polytech Fed Lausanne, Inst Neurosci, Lausanne, Switzerland
[3] CHU Vaudois, Div Surg Res, CH-1011 Lausanne, Switzerland
[4] CHU Vaudois, Gene Therapy Ctr, CH-1011 Lausanne, Switzerland
[5] Huddinge Univ Hosp, Karolinska Inst, Dept Neurotec, SE-14186 Lund, Sweden
[6] Wallenberg Neurosci Ctr, Sect Restorat Neurol, SE-22184 Lund, Sweden
[7] NsGene AS, DK-2750 Ballerup, Denmark
[8] Ajou Univ, Sch Med, Dept Neurosurg, Suwon 442721, South Korea
关键词
dopamine; xenotransplantation; GDNF; neurotrophic factor; polymer;
D O I
10.1016/j.brainresbull.2005.04.009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:135 / 142
页数:8
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