Analysis of preventive mechanisms of presbycusis using bone marrow transplantation and parabiosis

• Project/Area Number: 18591895
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kansai Medical University
• Principal Investigator: IWAI Hiroshi Kansai Medical University, 医学部, 准教授 (10232638)
• Co-Investigator(Kenkyū-buntansha): INABA Muneo 関西医科大学, 医学部, 准教授 (70115947)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥660,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: 老人性難聴 / 抗加齢 / ヘルパーT細胞 / 螺旋神経節 / モデルマウス / mRNA / 遺伝子 / 胸腺 / 免疫老化 / 難聴 / 老化 / サイトカイン / マイクロアレイ / CD4 / 並体結合 / 骨髄移植 / 免疫担当細胞

Research Abstract

当初の計画通り、骨髄移植および並体結合の手技を用いて、モデルマウスにおける老人性難聴の予防機序を検討した。またリンパ球接種や胸腺移植、さらに分子生物学的手法による検討を加えた。その結果、老人性難聴の進行には骨髄細胞のうちのTリンパ球、特にヘルパーT細胞(Th)が関係しており、骨髄移植だけでなくTh接種や、このリンパ球を産生する胸腺移植によって、老人性難聴の進行を予防・軽減できること(抗老人性難聴作用)が明らかとなった。そこで、若齢マウスと老齢マウスとの間でTh の機能を比較したところ、TRAF3(TNF receptorassociated factor 3)遺伝子など、4つの遺伝子の関与が示唆された。

Research Products

• [Journal Article] Maintenance of systemic immune functions prevents accelerated presbycusis (2008)
  • Author(s): Iwai H, et al.(員数6、1番目)
  • Journal Title: Brain Res 1208 Pages: 8-16
  • Peer Reviewed
• [Journal Article] Prevention of graft-versus-host disease by intrabone marrow injection of donor T cells : involvement of bone marrow stromal cells (2008)
  • Author(s): Miyake T, Inaba M, et al.(員数7、2番目)
  • Journal Title: Clin Exp Immunol 152 Pages: 153-162
  • Peer Reviewed
• [Journal Article] Subcutaneous adipose tissue-derived stem cells facilitate colonic mucosal recovery from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats (2008)
  • Author(s): Ando Y, Inaba M, et al.(員数8、2番目)
  • Journal Title: Inflamm Bowel Dis 14 Pages: 826-838
• [Journal Article] Preoperative concurrent chemoradiotherapy versus pre- and postoperative radiotherapy for advanced hypopharyngeal carcinoma : a singlecenter study (2008)
  • Author(s): Iwai H, et al.(員数6、1番目)
  • Journal Title: ANL 35 Pages: 235-241
  • Peer Reviewed
• [Journal Article] Long-term maintenance of donr-derived hemopoiesis by intra-bone marrow-bone marrow transplantation (2008)
  • Author(s): Omae M, Inaba M, Sakaguchi Y, Tsuda M, Miyake T, Fukui J, Iwai H, Yamashita T, Ikehara S.
  • Journal Title: Stem Cell Dev 17 Pages: 291-302
  • Peer Reviewed
• [Journal Article] Long-term donor-specific tolerance in rat cardiac allografts by intrabone marrow injection of donor bone marrow cells (2008)
  • Author(s): Guo K, Inaba M, et al.(員数16、2番目)
  • Journal Title: Transplantation 85 Pages: 93-101
• [Journal Article] Maintenance of Systemic Immune Functions Prevents Accelerated Presbycusis. (2008)
  • Author(s): Iwai H, Baba S, Omae M, Lee S, Yamashita T, Ikehara S
  • Journal Title: Brain Res 1208 Pages: 8-16
  • Peer Reviewed
• [Journal Article] Long-term maintenance of donr-derived hemopoiesis by intra-bone marrow-bone marrow transplantation. (2008)
  • Author(s): Omae M, Inaba M, Sakaguchi Y, Tsuda M, Miyake T, Fukui J, Iwai H, Yamashita T, Ikehara S
  • Journal Title: Stem Cell Dev 17 Pages: 291-302
  • Peer Reviewed
• [Journal Article] Maintenance of systemic immune functions prevents accerelated presbycusis (2008)
  • Author(s): Iwai H, Baba S, Omae M, Lee S, Yamashita T, Ikehara S
  • Journal Title: Brain Research 1203 Pages: 8-16
  • Peer Reviewed
• [Journal Article] Treatment of streptozotocin- induced diabetes mellitus in mice by intra-bone marrow bone marrow transplantation plus portal vein injection of beta cells induced from bone marrow cells (2007)
  • Author(s): Li M, Inaba M, et al.(員数6、2番目)
  • Journal Title: Int J Hematol 86 Pages: 438-445
  • Peer Reviewed
• [Journal Article] Kimura's disease : diagnosis and prognostic factors (2007)
  • Author(s): Iwai H,et al.(員数8、1番目)
  • Journal Title: Otolaryngol Head Neck Surg 137 Pages: 306-311
  • Peer Reviewed
• [Journal Article] Extensive studies on perfusion method plus intra-bone marrow-bone marrow transplantation using cynomolgus monkeys (2007)
  • Author(s): Inaba M, et al.(員数30、1番目)
  • Journal Title: Stem Cells 25 Pages: 2098-2103
  • Peer Reviewed
• [Journal Article] Prevention of graft-versus-host disease by intra-bone marrow injection of donor T cells (2007)
  • Author(s): Fukui J, Inaba M, et al.(員数11、2番目)
  • Journal Title: Stem Cells 25 Pages: 1595-1601
  • Peer Reviewed
• [Journal Article] Induction of senile osteoporosis in normal mice by intra-bone marrow-bone marrow transplantation from osteoporosis-prone mice (2007)
  • Author(s): Ueda Y, Inaba M, et al.(員数10、2番目)
  • Journal Title: Stem Cells 25 Pages: 1356-1363
  • Peer Reviewed
• [Journal Article] 全身免疫能操作による進行性蝸牛障害の予防と治療 (2007)
  • Author(s): 岩井 大
  • Journal Title: Current Article 耳喉頭頸 79 Pages: 899-905
• [Journal Article] 全身免疫能操作による進行性蝸牛障害の予防と治療 (2007)
  • Author(s): 岩井 大
  • Journal Title: 耳喉頭頸 79 Pages: 899-905
• [Journal Article] Early acquisition of esophageal phonation following tracheoesophageal phonation (2006)
  • Author(s): Iwai H, et al.(員数5、1番目)
  • Journal Title: Acta Oto-laryngologica. Acta Otolaryngol 126 Pages: 764-768
  • Peer Reviewed
• [Journal Article] Transfer of accerelated presbycusis by transplantation of bone marrow cells from senescence-accelerated mice (2006)
  • Author(s): Baba S, Iwai H, Inaba M, Kawamoto K, Omae M, Yamashita T, Ikehara S.
  • Journal Title: Brain Res 1120 Pages: 93-99
  • Peer Reviewed
• [Journal Article] Transfer of accelerated presbycusis by transplantation of bone marrow cells from senescence-accelerated mice (2006)
  • Author(s): Baba S
  • Journal Title: Brain Res 1120 Pages: 93-99
• [Presentation] 加齢性聴覚機能における全身免疫の関与の検討 (2008)
  • Author(s): 大前麻理子、岩井 大、馬場奨、李進隆、山下敏夫
  • Organizer: 第109回日本耳鼻咽喉科学会
  • Place of Presentation: 大阪
• [Presentation] シンポジウムー難聴の予防と治療:骨髄移植によるアプローチAVC(Audio Visual Disability)に対する抗加齢医学のサイエンス (2007)
  • Author(s): 岩井 大
  • Organizer: 第78日本抗加齢医学会
  • Place of Presentation: 京都
  • Year and Date: 2007-07-21
• [Presentation] 蝸牛機能に対する全身免疫機能の作用の検討 (2007)
  • Author(s): 大前麻理子、岩井 大、山下敏夫
  • Organizer: 第17回日本耳科学会
  • Place of Presentation: 福岡
• [Presentation] Prevention of accelerated presbycusis by maintenance of systemic immune functions (2007)
  • Author(s): Iwai H, et al.(員数6、1番目)
  • Organizer: 44th Inner Ear Biology Workshop
  • Place of Presentation: London
• [Presentation] Interaction between cochlear cells and bone marrow cells (2007)
  • Author(s): Baba S, Iwai H, et al.(員数6、2番目)
  • Organizer: 44th Inner Ear Biology Workshop
  • Place of Presentation: London
• [Presentation] Relationship between accelerated presbycusis and immunosenescence (2007)
  • Author(s): Lee S, Iwai H, et al.(員数6、2番目)
  • Organizer: 44th Inner Ear Biology Workshop
  • Place of Presentation: London
• [Presentation] シンポジウム-難聴の予防と治療 : 骨髄移植によるアプローチ (2007)
  • Author(s): 岩井 大
  • Organizer: AVC(Audio Visual Disability)に対する抗加齢医学のサイエンス。第7回日本抗加齢医学会
  • Place of Presentation: 京都
• [Presentation] 異系骨髄内骨髄移植法を用いたマウス造血前駆細胞の解析 (2006)
  • Author(s): 大前麻理子、稲葉宗夫、上田祐輔、坂口雄沢、津田雅庸、福井淳一、李銘、郭可泉、三宅岳、岩井 大、山下敏夫、池原進
  • Organizer: 第36回日本免疫学会
  • Place of Presentation: 大阪
• [Presentation] Evidence of treatment of autoimmune hearing loss by reconstitution of systemic immune system (2006)
  • Author(s): Lee S, Iwai H, Baba S, Otani M, Inaba M, Omae M, Ikeahara S, Yamashita T.
  • Organizer: 43rd Inner Ear Biology Workshop
  • Place of Presentation: Monpellier, France
• [Presentation] Relation between acceleration of age-related hearing loss and bone marrow cells from senescence-prone donors (2006)
  • Author(s): Baba S, Iwai H, Lee S, Otani M, Inaba M, Omae M, Kawamoto K, Ikehara S, Yamashita T.
  • Organizer: 43rd Inner Ear Biology Workshop
  • Place of Presentation: Monpellier, France
• [Presentation] Transfer of autoimmune inner ear disorder by bone marrow transplantation (2006)
  • Author(s): Otani M, Iwai H, Lee S, Baba S, Inaba M, Ikehara S, Yamashita T.
  • Organizer: 43rd Inner Ear Biology Workshop
  • Place of Presentation: Monpellier, France
• [Presentation] Role of systemic immune system in survival of the spiral ganglion cells (2006)
  • Author(s): Iwai H, Baba S, Lee S, Otani M, Inaba M, Omae M, Ikehara S, Yamashita T.
  • Organizer: 43rd Inner Ear Biology Workshop
  • Place of Presentation: Monpellier, France