Transplantation of a polymer-encapsulated cell line genetically engineered to release NGF.
The delivery of nerve growth factor (NGF) to the lateral ventricle of a fimbria-fornix-lesioned rat prevents the lesion-induced reduction in choline acetyltransferase (ChAT) expression by medial septal cells. Although delivery has been achieved through neural grafting of genetically engineered cell lines which release NGF, transplanted cells have grown beyond the implantation site and formed tumors. The encapsulation of cells within a permselective polymer capsule prior to transplantation allows cell growth only within the capsule space, while allowing molecular exchange between the host tissue and enclosed cells. Rat fibroblasts from the parent cell line (R208F) or fibroblasts genetically modified to produce NGF (R208N.8) were loaded within a thermoplastic hollow fiber-based capsule. Only the capsules loaded with the genetically engineered cells released measurable amounts of NGF in culture. Adult rats received unilateral aspirative fimbria-fornix lesions, followed by intraventricular implantation of a R208F capsule (n = 6) or a R208N.8 capsule (n = 6). After 2 weeks, rats receiving encapsulated cells showed no undue reaction to the implants. With both cell types, the cells remained viable and confined to the capsule space. R208N.8 capsules released sufficient NGF to prevent the lesion-induced loss of septal ChAT expression, whereas R208F capsules did not. This study suggests that encapsulated genetically engineered cells can provide an efficient means for future applications involving delivery of neurotrophic factors.
Hoffman
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D
Section of Artificial Organs, Biomaterials, and Cellular Technology, Brown University, Providence, Rhode Island 02912.
Breakefield
X O
XO
Short
M P
MP
Aebischer
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P
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D002214:Capsules; D002460:Cell Line; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation*; D005818:Genetic Engineering; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D016716:PC12 Cells / Q000502:physiology; D011108:Polymers; D012688:Septum Pellucidum / Q000166:cytology / Q000378:metabolism; D014180:Transplantation / Q000379:methods*
D002214:Capsules; D009414:Nerve Growth Factors; D011108:Polymers; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase