| Project/Area Number |
11671712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kansai Medical University |
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Principal Investigator |
IWAI Hiroshi Kansai Medical University,Faculty of Medicine,Assistant Professor, 医学部, 講師 (10232638)
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| Co-Investigator(Kenkyū-buntansha) |
INABA Muneo Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70115947)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | autoimmune hearing loss / presbycusis / hematopoietic stem cells / immunocompetent cell / systemic immune system / blood-labyrinthine barrier / organ-specific autoimmune disease / bone marrowtransplantation / 免疫能 / SPF / 免疫複合体 / conventional / 聴性脳幹反応 / 免疫機能 / 早期老人性難聴 / フローサイトメトリー / マイトジェン / TUNNEL法 / 螺旋神経節 / apoptosis |
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| Research Abstract |
In the present study, we have investigated mechanisms of sensorineural hearing loss and its treatments for prevention and cure in animal models. We have first demonstrated using an animalmodel for graft-versus-host disease the existence of proliferating cells in the donor T cells infiltrating the perisaccular region. These findings suggest that immunocompetent cells in the systemic circulation infiltrate the endolymphatic sac or inner ear through the blood-labyrinthine and blood-endolymphatic barrlers and proliferate locally as a consequence of the immune response. They also indicate that Meniere's disease is an organ-specific autoimmune disease and similar to chronic thyroiditis and juvenile diabetic mellitus. We have also indicated that presbycusus (age-related hearing loss) is accelerated in an animal model for accelerated senescence including the age-related acceleraation of both immunological dysfunction and hearing loss when the immune function is impaired as a consequence of bre
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eding the animal under pathogenic environment. These results support our theory of relation between the systemic immune system and local immune system in the inner ear and also indicate that some types of inner ear diseases do not result from defects in the inner ear but do from defects in the hematopoletic stem cells (HSCs) and immunocompetent cells derived from the HSCs, which manage the systemic immune system.
These findings have prompted us to prevent or cure the age-related hearing loss or autoimmune hearing loss using bone marrow transplantation (BMT) followed by irradiation, which reconstitute the host immunocompetent cells and systemic immune system as well as host HSCs by the normal donor cells. The results of study indicate preventive or curative effect of BMT upon those hearing losses and confirme that some types of inner ear diseases cause by dysfunction of HSCs. If this is the case, either allogeneic BMT, which replaces abnormal HSCs with normal HSCs and reconstructs a normal immune system in the hosts, or autologous BMT using genetically modified bone marrow cells, could become a new strategy for the treatment of inner ear disease including sensorineural hearing loss. Less
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