| Project/Area Number |
20390445
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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 | Juntendo University |
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Principal Investigator |
IKEDA Katuhisa Juntendo University, 医学部, 教授 (70159614)
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| Co-Investigator(Kenkyū-buntansha) |
MINOWA Osamu 理化学研究所, 上級研究員 (00181967)
TAKESHI Kusunoki 順天堂大学, 医学部, 准教授 (30248025)
FURUKAWA Masayuki 順天堂大学, 医学部, 准教授 (20359524)
YOKOI Hidenori 順天堂大学, 医学部, 准教授 (80317487)
KOIKE Takuji 電気通信大学, 電気通信学部, 准教授 (10282097)
KAMIYA Kazusaku 順天堂大学, 医学部, 講師 (10374159)
KAKEHATA Seiji 順天堂大学 (90261619)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | GJB2 / 難聴 / ノックアウトマウス / コルチ器 / 内耳 / 蝸牛 / 内リンパ / 半規管 / アデノウイルスベクター / アデノ随伴ウイルスベクター / 聴性脳幹反応 / GJB2遺伝子 / 遺伝子導入 / ウイルスベクター / アデノウイル / アデノ随伴ウイル |
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| Research Abstract |
Congenital deafness affects about 1 in 1000 children and the half of them have genetic background such as Connexin26 gene mutation. The strategy to rescue such heredity deafness has not been developed yet. Recently, a number of clinical studies for cell therapy have been reported and clinically used for several intractable diseases. Inner ear cell therapy for sensorineural hearing loss also has been studied using some laboratory animals, although the successful reports for the hearing recovery accompanied with supplementation of the normal functional cells followed by tissue repair, recovery of the cellular/molecular functions were still few. Previously, we developed a novel animal model for acute sensorineural hearing loss due to fibrocyte dysfunction and performed cell therapy with bone marrow mesenchymal stem cells (MSC) as supplementation of cochlear fibrocytes functioning for cochlear ion transport. MSC has been known to have little risk for carcinogenesis compared with embryonic
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stem (ES) cell and induced pluripotent stem (iPS) cell. We injected MSC into the lateral semicircular canal and a number of these stem cells were then detected in the injured area in the lateral wall. The transplanted animals showed a significantly higher hearing recovery ratio than controls. We analyzed the machinery of this stem cell induction to the targeted site in cochlea and found that monocyte chemotactic protein 1 (MCP1) and chemokine (C-C motif) receptor 2 (CCR2) played important roles for this cell induction. To enhance the MSC induction in cochlea, we developed a novel transplant strategy by induction of MCP1 expression in host cochlear tissue and forced expression of CCR2 in MSC. Furthermore, we developed a novel mouse model for Connexin26 mutation as most frequent heredity deafness in human. With these animal models, the developed stem cells and the novel strategy to enhance the stem cell induction, we examined to establish an efficient stem cell therapy to cochlear target site followed by recovery of hearing function in heredity deafness. Less
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