1998 Fiscal Year Final Research Report Summary
Pain treatment with xenogeneic cells transfected with drug inducible opiate gene
| Project/Area Number |
09557118
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
SAITOH Youichi Osaka University Medical School, Assistant Professor, 医学部, 助手 (20252661)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Toru Osaka University Medical School, Professor, 医学部, 教授 (20135700)
WATAHIKI Masanori NIPPON GENE Co Ltd., Research and Development Div., Director, 研究開発部, 部長
EGUCHI Yutaka Osaka University Medical School, Associate Professor, 医学部, 助教授 (20243206)
ARITA Norio Osaka University Medical School, Lecturer, Instructor, 医学部, 講師 (80159508)
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| Project Period (FY) |
1997 – 1998
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| Keywords | pain / beta-endorphin / polymer capsule / ex vivo gene therapy / xenograft / Tet-On system / tetracycline / doxycycline |
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| Research Abstract |
We previously reported that xenogeneic cells, carrying the proopiomelanocortin (POMC) gene coding the precursor of the ACTH and 13-endorphin in a polymer capsule transplanted into the cerebrospinal fluid (CSF) space of rats, secrete b-endorphin and reduce their pain. However, the activities of transplanted cells were barely controlled by exogenous agents. The Tet-On system, one of the transcriptional transactivators, which requires certain tetracycline derivatives for specific DNA binding, has been developed and considered to be applicable for the control of the transplanted cells. The pUHD1O-3-POMC and pUHD172-lneo were co-transfected to Neuro2A, a mouse neuroblastoma cell line, named Neuro2A-POMC.Neuro2A cells carrying the doxycycline-inducible POMC gene expressed and secreted ACTH upon addition of the doxycycline in vitro in a dose-dependent manner. The encapsulated and transplanted cells in the CSF space of rats were stimulated by four intraperitoneal injections of doxycycline, and found to express ACTH after subsequence 36-hour incubation in vitro, depending on the amounts of injected doxycycline. These findings indicate that gene expression in xenogeneic cells in the CSF space can be manipulated by injection a relatively harmless drug, and suggest that our system is applicable to cell transplantation therapy in central nervous system diseases requiring well-controlled substance delivery.
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