Gene delivery to the inner ear by transplantation of ex vivo gene-manipulated cells
| Project/Area Number |
16390488
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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 | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAGAWA Takayuki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (50335270)
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| Co-Investigator(Kenkyū-buntansha) |
KITA Tomoko RIKEN Center for Developmental Biology, Sensory Development, Researcher, 発生・再生科学総合研究センター・感覚器官発生研究チーム, 訪問研究員 (20362519)
FUNABIKI Kazuo Osaka Bioscience Institute, Systems Biology, Researcher, システムズ生物学部門, 研究員 (00301234)
ASATO Ryo Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70283603)
藤野 清大 京都大学, 医学研究科, 助手 (50359832)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | Cell transplantation / Gene therapy / inner ear / Neurotrophic factor / Bone marrow stromal cell / Spiral ligament / 再生医療 / 感音難聴 / 骨髄由来細胞 |
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| Research Abstract |
Sensorineural hearing loss (SNHL) is a common disability, but treatment options are currently limited to cochlear implants and hearing aids. Studies are therefore being conducted to provide alternative means of biological therapy, including gene therapy. Safe and effective methods of gene delivery to the cochlea need to be developed to facilitate the clinical application of these therapeutic treatments for hearing loss. In this study, we examined the potential of cell-gene therapy with non-viral vectors for delivery of therapeutic molecules into the cochlea. NIH3T3 cells were transfected with the brain-derived neurotrophic factor (BDNF) gene using lipofection and then transplanted into the mouse inner ear. Immunohistochemistry and western blotting demonstrated the survival of grafted cells in the cochlea for up to four weeks after transplantation. No significant hearing loss was induced by the transplantation procedure. A BDNF-specific enzyme-linked immunosorbent assay revealed a significant increase in BDNF production in the inner ear following transplantation of engineered cells. These findings indicate that cell-gene delivery with non-viral vectors may be applicable for the local, sustained delivery of therapeutic molecules into the cochlea. We examined the potential of bone-marrow stromal cell (BMSC) as a vehicle to deliver genes or their products into inner ear tissues. BMSCs labelled with enhanced green fluorescent protein were injected into the periplymphatic space of normal cochleae in mice. Histological analysis 2 weeks after transplantation demonstrated that transplanted cells settled within the cochlear tissues, especially in the spiral ligament, although most transplants were located in the perilymphatic space. These findings indicate the potential of BMSCs for delivering genes in the spiral ligament.
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Report
(4 results)
Research Products
(42 results)
