Genetically modified PC12 brain grafts: Survivability and inducible nerve growth factor expression

D. C. Rohrer; G. Nilaver; V. Nipper; C. A. Machida

doi:10.1016/0963-6897(95)02023-3

Genetically modified PC12 brain grafts: Survivability and inducible nerve growth factor expression

D. C. Rohrer
, G. Nilaver
, V. Nipper
, C. A. Machida

Integrative Biosciences

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neurodifferentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.

Original language	English (US)
Pages (from-to)	57-68
Number of pages	12
Journal	Cell Transplantation
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/0963-6897(95)02023-3
State	Published - 1996

Funding

culture materials were provided by the ORPRC Cell Culture Core Facility. D.C.R. has recently completed his Chief Residency of Neurosurgery at the OHSU, and is now a practicing physician and neurosurgeon with Microneurosurgical Consultants, P.C. G.N. was supported by a Grant from the Council for Tobacco Research, USA, Inc. C.A.M. is supported by NIH RR00163, and is an American Heart Association Established Investigator.

Funders	Funder number
Council for Tobacco Research, USA, Inc.
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
National Center for Research Resources	P51RR000163
American Heart Association/American Stroke Association

Keywords

Brain grafts
Nerve growth factor
Neural transplantation
Parkinson's disease

ASJC Scopus subject areas

Biomedical Engineering
Cell Biology
Transplantation

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10.1016/0963-6897(95)02023-3

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title = "Genetically modified PC12 brain grafts: Survivability and inducible nerve growth factor expression",

abstract = "Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neurodifferentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.",

keywords = "Brain grafts, Nerve growth factor, Neural transplantation, Parkinson's disease",

author = "Rohrer, \{D. C.\} and G. Nilaver and V. Nipper and Machida, \{C. A.\}",

note = "Funding Information: culture materials were provided by the ORPRC Cell Culture Core Facility. D.C.R. has recently completed his Chief Residency of Neurosurgery at the OHSU, and is now a practicing physician and neurosurgeon with Microneurosurgical Consultants, P.C. G.N. was supported by a Grant from the Council for Tobacco Research, USA, Inc. C.A.M. is supported by NIH RR00163, and is an American Heart Association Established Investigator.",

year = "1996",

doi = "10.1016/0963-6897(95)02023-3",

language = "English (US)",

volume = "5",

pages = "57--68",

journal = "Cell Transplantation",

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T2 - Survivability and inducible nerve growth factor expression

AU - Rohrer, D. C.

AU - Nilaver, G.

AU - Nipper, V.

AU - Machida, C. A.

N1 - Funding Information: culture materials were provided by the ORPRC Cell Culture Core Facility. D.C.R. has recently completed his Chief Residency of Neurosurgery at the OHSU, and is now a practicing physician and neurosurgeon with Microneurosurgical Consultants, P.C. G.N. was supported by a Grant from the Council for Tobacco Research, USA, Inc. C.A.M. is supported by NIH RR00163, and is an American Heart Association Established Investigator.

PY - 1996

Y1 - 1996

N2 - Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neurodifferentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.

AB - Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neurodifferentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.

KW - Brain grafts

KW - Nerve growth factor

KW - Neural transplantation

KW - Parkinson's disease

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Genetically modified PC12 brain grafts: Survivability and inducible nerve growth factor expression

Abstract

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Keywords

ASJC Scopus subject areas

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