| Project/Area Number |
14571648
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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, Dept.of Otolaryngology, Assistant Professor, 医学部, 講師 (10232638)
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| Co-Investigator(Kenkyū-buntansha) |
INABA Muneo Kansai Medical University, First Dept.of Pathology, Associate Professor, 医学部, 助教授 (70115947)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | spiral ganglion cell / degeneration / regeneration / stria vascularis / sensorineural hearing loss / bone marrow transplantation / GEP / immunocompetent cell / 蝸牛 / 老人性難聴 / 自己免疫 / 全身免疫機能 / シスプラチン / 過大音響負荷 / green fluorescence protein / トランスジェニックマウス / 免疫 |
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| Research Abstract |
The aim of the current study was to evaluate function of hemopoietic stem cells (HSCs) or immunocompetent cells differentiated from those stem cells in regeneration or degeneration of the cochlear cells associated with age-related sensorineural hearing loss (SNHL).
As animal models of accelerated age-related SNHL, two murine substrains, the MRL/lpr mouse and SAMP1 mouse were used. As normal mice which show slow presbycusis, BALB/c, C57BL/6, or GFP (green fluorescence protein) mice which is C57BL/6 transgenic mice with GFP DNA were used.
Bone marrow cells including HSCs were inoculated intravenously as conventional bone marrow transplantation (BMT), or into bone marrow cavity (intra-BMT) which can maintain the host immune function similar to the function of pre-transplantation.
The results indicated that SNHL and cochlear degeneration in both animal models do not result from defects in the cochlea but do from defects in HSCs and immunocompetent cells derived from the HSCs because transplan
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tation of bone marrow from normal mice prevented or recovered the SNHL with degeneration of the stria vascularis in MRL/lpr mice, or of the spiral ganglion (SG) cells in SAMP1 mice, and also because transplantation of bone marrow from the murine models of SNHL with cochlear pathology caused the same hearing loss and pathology in the normal mice.
The relationship between presbycusis and the immune system was also analyzed using SAMP1 mice. When the immune functions were impaired, these mice showed aggressive development of SNHL and degeneration of the SG. These findings indicate that not only the gene backgrounds but also immune functions affect the neurogeneration system in SAMP1 mice.
Immunofluorescence study indicated that donor cells including HSCs and immunocompetent cells were not observed in the cochlea of the SNHL mice which had been transplanted bone marrow cells from the GEP mice and prevented SNHL and degeneration of the cochlea. In addition, both MRL/lpr and SAMP1 mice showed age-related dysfunctions of Th cells. These findings taken together indicate that cochlear cells are not regenerated or maintained by local infiltrated cells including HSCs and immunocompetent cells but are managed by humoral factors, through the blood-inner ear barrier, such as cytokines released by systemic Th cells, which may play key role of therapy for chronic development of SNHL. Less
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