Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line—derived neurotrophic factor in patients with Parkinson's disease

Report of two cases and technical considerations

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✓ The authors have studied the ability of glial cell line—derived neurotrophic factor (GDNF) to promote survival of human fetal dopaminergic tissue after a storage period of 6 days and subsequent implantation into the human putamen. The results indicate that GDNF promotes survival of stored dopaminergic cells. Cells stored without GDNF had a 30.1% decrease in survival time compared with those exposed to GDNF. Two patients with Parkinson's disease received bilateral putaminal implants of fetal dopaminergic cells exposed to GDNF for 6 days and showed enhancement of graft survival as assessed by positron emission tomography scanning. A mean increase of 107% in putaminal fluorodopa uptake from baseline values was observed 12 months postgrafting.

Article Information

Address reprint requests to: Ivar Mendez, M.D., Ph.D., Division of Neurosurgery, QEII Health Sciences Centre, New Halifax Infirmary, 1796 Summer Street, Room #3806, Halifax, Nova Scotia, B3H 3A7, Canada. email: mendez@is.dal.ca.

© AANS, except where prohibited by US copyright law.

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Figures

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    Bar graph showing the percentage of TH-positive neurons in cell cultures of human VM tissue. Cell cultures were made of fresh VM tissue and tissue stored for 6 days with and without GDNF. The results were compared relative to the cell stored with GDNF. * p = 0.006.

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    A: Preoperative and 1-year postoperative PET scans realigned to MR images in two patients (1, 2) who underwent implantation with stored VM tissue exposed to GDNF. A significant increase in putaminal [18F]fluorodopa Ki was observed bilaterally in the two patients 1 year after implantation. B: Bar graph showing preoperative and 1-year postoperative mean regional [18F]fluorodopa Ki values. C: Bar graph showing percentage of change of normal uptake in the area of the graft, putamen, and caudate in the two patients reported. * p = 0.03.

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