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頭頸部・感覚器外科学顎顔面外科学

概要

昭和41年に口腔外科学講座が開設されてから50年がたち、その前身の診療科時代を含めれば約100年の歴史があります。先人たちの地道な努力のおかげで環境、人材ともに恵まれ、学内に約50名、学外の関連施設にも約50名が研究に、臨床に切磋琢磨しています。おもな研究内容は悪性腫瘍、再生医療などに関するものであり、その成果は質、量とも一定の評価を得ています。とくに再生医療の分野では基礎から臨床までをつなげる、いわゆるトランスレーショナルリサーチや先進医療、産業化の実績があります。

研究プロジェクト

1. 再生医療

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i) 培養細胞による組織再生
失ったからだの一部をなおすには他の部位からとってきた組織を移植する必要がありますが、これはたいへんなことでした。そこでそれにかわるものとして再生医療が注目されています。これはからだの中からほんのすこしの細胞を取り出し、からだの外で培養して増やしてから、またからだに戻し必要な組織をつくらせるというものです。当研究室には粘膜・皮膚や骨の欠損、脊髄損傷などの研究で実績があります。皮膚では企業への技術移転、骨では先進医療として実施がかないました。先進医療B「骨髄由来間葉系細胞による顎骨再生療法」は自分のからだから取り出した骨髄の細胞と血液成分を組み合わせて骨を再生させるものであり、全国で唯一の実施医療機関として厚生労働省の承認を得ています。


 

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ii) 培養上清による組織再生・組織傷害治療
移植した細胞は直接的に組織をつくるだけでなく、いろいろな因子を分泌しからだ中の細胞を呼び寄せて組織を間接的につくらせることが明らかになってきました。そこでこの因子が培養液の上清中に多く含まれていることに着目し、培養細胞の代わりにこの培養上清をつかって組織を再生させる研究をしています。自分の細胞をとらなくてよい、細胞移植が必要ないなどから、安全性、利便性、経済性などの点で上記の「培養細胞による組織再生」の課題を解決するものとして期待されています。なかでも注目されているのは歯髄細胞がつくる因子群で、骨や歯周組織、神経などの組織再生だけでなく、抗炎症、免疫抑制などの多面的な効果があることがわかり、それを糖尿病、アルツハイマー型認知症、リウマチ性関節炎、肝線維症、急性心筋梗塞、自己免疫性脳脊髄炎などの動物モデルで示しています。


 

iii) 合成された因子による組織再生
上記の「培養上清」中に含まれる因子のうち何が効いたのかがわかれば、それを合成し薬としてつかうことができるでしょう。この取り組みは 成果を上げつつあり、さらに実用化への障壁を下げるものとして期待されています。

2. 新規扁平上皮癌マーカーの開発

口腔癌に多い扁平上皮癌に特異的に高い値を示す腫瘍マーカーがすでに利用されていますが、早期癌まではわからないのが課題でした。そこで口腔癌の早期発見、再発予知などに有用な新しい腫瘍マーカーが探し求められています。当研究室では腫瘍病理学の研究室と共同で細胞膜タンパク質であるCD109に注目し研究を進めています。これにより口腔扁平上皮癌をその前触れ状態から発見できる途が開かれつつあります。現在、検体採取が簡単で測定感度が鋭敏な方法を探索しています。

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教員

構成員名役職所属
日比 英晴 教授 医学系研究科頭頸部感覚器外科学講座 顎顔面外科学
山本 憲幸 講師 医学部附属病院 歯科口腔外科
西川 雅也 病院助教 医学部附属病院 歯科口腔外科
土屋 周平 助教 医学部附属病院 歯科口腔外科
坂倉 寬紀 助教 医学系研究科頭頸部感覚器外科学講座 顎顔面外科学
岡部 一登 助教 医学部附属病院 歯科口腔外科
藤尾 正人 助教 医学系研究科頭頸部感覚器外科学講座 顎顔面外科学
酒井 陽 助教 医学系研究科頭頸部感覚器外科学講座 顎顔面外科学
原 憲史 助教 医学部附属病院 歯科口腔外科

研究実績

  • 2018年
    1. Okabe K, Kaneko R, Kawai T, Mochiduki D, Tsuchiya S, Hibi H.Ophthalmoplegia considered to be Tolosa-Hunt syndrome: A case report. J Oral Maxillofac Surg Med Pathol, in Press.
    2. Sato K, Hayashi Y, Yamamoto N, Ichimura N, Hibi H. A case of post-transplant lymphoproliferative disorders that developed ten years after living renal transplantation in the parotid gland region.J Oral Maxillofac Surg Med Pathol, in Press.
    3. Ichimura N, Yamamoto N, Nishikawa M, Sakakura H, Kano F, Sato K, Yamaguchi S, Hibi, H. Human papillomavirus-related carcinogenesis in oral cancer. Oral Science in Japan, 2017: 83-84.
    4. Tsuchiya S, Sugimoto K, Kamio H, Okabe K, Kuroda K, Okido M, Hibi H. Kaempferol-immobilized titanium dioxide promotes formation of new bone: effects of loading methods on bone marrow stromal cell differentiation in vivo and in vitro. Int J Nanomedicine, 2018; 13: 1665-1676.
  • 2017年
    1. Ichimura N, Yamamoto N, Nishikawa M, Furue H, Kondo Y, Hibi H. Notch3 is frequently downregulated in oral cancer. J Oral Maxillofac Surg Med Pathol, 2017; 29: 504-510.
    2. Katagiri W, Watanabe J, Toyama N, Osugi M, Sakaguchi K, Hibi H. Clinical study of bone regeneration by conditioned medium from mesenchymal stem cells after maxillary sinus floor elevation. Implant Dent, 2017; 26: 607-612.
    3. Fujio M, Xing Z, Sharabi N, Xue Y, Yamamoto A, Hibi H, Ueda M, Fristad I, Mustafa K. Conditioned media from hypoxic-cultured human dental pulp cells promotes bone healing during distraction osteogenesis. J Tissue Eng Regen Med, 2017; 11: 2116-2126.
    4. Ogata K, Katagiri W, Hibi H. Secretomes from mesenchymal stem cells participate in the regulation of osteoclastogenesis in vitro. Clin Oral Investig, 2017; 21: 1979-1988.
    5. Sugimoto K, Tsuchiya S, Hara K, Matsushita Y, Hibi H. Osteoradionecrosis of the jaw caused by periapical periodontitis: A case report. J Oral Maxillofac Surg Med Pathol, 2017; 29: 328-333.
    6. Katagiri W, Sakaguchi K, Kawai T, Wakayama Y, Osugi M, Hibi H. A defined mix of cytokines mimics conditioned medium from cultures of bone marrow-derived mesenchymal stem cells and elicits bone regeneration. Cell Prolif, 2017; 50: e12333.
    7. Ito T, Ishigami M, Matsushita Y, Hirata M, Matsubara K, Ishikawa T, Hibi H, Ueda M, Hirooka Y, Goto H, Yamamoto A. Secreted ectodomain of SIGLEC-9 and MCP-1 synergistically improve acute liver failure in rats by altering macrophage polarity. Sci Rep, 2017; 7: 44043.
    8. Kano F, Matsubara K, Ueda M, Hibi H, Yamamoto A. Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and MCP-1 synergistically regenerate transected rat peripheral nerves by altering macrophage polarity. Stem Cells, 2017; 35: 641-653.
    9. Sakaguchi K, Katagiri W, Osugi M, Kawai T, Sugimura-Wakayama Y, Hibi H. Periodontal tissue regeneration using the cytokine cocktail mimicking secretomes in the conditioned media from human mesenchymal stem cells. Biochem Biophys Res Commun, 2017; 484: 100-106.
  • 2016年
    1. Hirata M, Ishigami M, Matsushita Y, Ito T, Hattori H, Hibi H, Goto H, Ueda M, Yamamoto A. Multifaceted therapeutic benefits of factors derived from dental pulp stem cells for mouse liver fibrosis. Stem cells Transl Med, 2016; 5: 1416-1424.
    2. Shimojima C, Takeuchi H, Jin S, Parajuli B, Hattori H, Suzumura A, Hibi H, Ueda M, Yamamoto A. Conditioned medium from the stem cells of human exfoliated deciduous teeth ameliorates experimental autoimmune encephalomyelitis. J Immunol, 2016; 15: 4164-4171.
    3. Katagiri W, Osugi M, Kawai T, Hibi H. First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head Face Med, 2016; 12: 5.
    4. Hibi H. Clinical review of bone regenerative medicine and maxillomandibular reconstruction. Oral Sci Int, 2016; 13: 15-19.
    5. Sakakura H, Mii S, Hagiwara S, Kato T, Yamamoto N, Hibi H, Takahashi M, Murakumo Y. CD109 is a component of exosome secreted from cultured cells. Biochem Biophys Res Commun, 2016; 469: 816-822.
    6. Ishikawa J, Takahashi N, Matsumoto T, Yoshioka Y, Yamamoto N, Nishikawa M, Hibi H, Ishiguro N, Ueda M, Furukawa K, Yamamoto A. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis. Bone, 2016; 83: 210-219.
    7. Sugimoto K, Tsuchiya S, Omori M, Matsuda R, Fujio M, Kuroda K, Okido M, Hibi H. Proteomic analysis of bone proteins adsorbed onto the surface of Etanium dioxide. Biochem Biophys Rep, 2016; 7: 316-322.
    8. Hishida S, Ozaki N, Honda T, Shigetomi T, Ueda M, Hibi H, Sugiura Y. Atrophy of submandibular gland by the duct ligaEon and a blockade of SP receptor in rats. Nagoya J Med Sci, 2016; 78: 215-227.
    9. Tsuchiya S, Sugimoto K, Omori M, Matsuda R, Fujio M, Hibi H. Mandibular osteomyeliEs implicated in infliximab and periapical periodonEEs: A case report. J Oral Maxillofac Surg Med Pathol, 2016; 28: 410-415.
    10. Yokota T,Tachibana H,Konishi T,Yurikusa T,Hmauchi S,Sakai K,Nishikawa M,Suzuki M,Naganama Y,Hagihara T,Tsumaki H,Kubo T,Sato M,Tagura M,Morita S,Eguchi T,KubotaK,Zenda S.Multicenter phase II study of an oral care program for patients with head and neck cancer receiving chemoradiotherapy.Support Care Cancer,2016; 24: 3029-3036.
  • 2015年
    1. Yamaguchi S, Shibata R, Yamamoto N, Nishikawa M, Hibi H, Tanigawa T, Ueda M, Murohara T, Yamamoto T. Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion. Sci Rep, 2015; 5: 16295.
    2. Izumoto-Akita T, Tsunekawa S, Yamamoto A, Uenishi E, Ishikawa K, Ogata H, Iida A, Ikeniwa M, Hosokawa K, Niwa Y, Maekawa R, Yamauchi Y, Seino Y, Hamada Y, Hibi H, Arima H, Ueda M, Oiso Y. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic beta-cell function. BMJ Open Diab Res Care, 2015; 3: e000128.
    3. Katagiri W, Osugi M, Kinoshita K, Hibi H. Conditioned medium from mesenchymal stem cells enhances early bone regeneration after maxillary sinus floor elevation in rabbits. Implant Dent, 2015; 24: 657-663.
    4. Katagiri W, Osugi M, Kawai T, Hibi H. Secreted frizzled-related protein promotes bone regeneration by human bone marrow-derived mesenchymal stem cells. Int J Mol Sci, 2015; 16: 23250-23258.
    5. Tsuchiya S, Ohmori M, Hara K, Fujio M, Ikeno M, Hibi H, Ueda M. An experimental study on guided bone regeneration using a polylactide-co-glycolide membrane-immobilized conditioned medium. Int J Oral Maxillofac Implants, 2015; 30: 1175-1186.
    6. Mita T, Furukawa-Hibi Y, Takeuchi H, Hattori H, Yamada K, Hibi H, Ueda M, Yamamoto A. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer's disease. Behav Brain Res, 2015; 293: 189-197.
    7. Sugimura Y, Katagiri W, Osugi M, Kawai K, Ogata K, Sakaguchi K, Hibi H. Peripheral nerve regeneration by secretomes of stem cells from human exfoliated deciduous teeth. Stem Cells Dev, 2015; 24: 2687-2699.
    8. Omori M, Tsuchiya S, Hara K, Kuroda K, Hibi H, Okido M, Ueda M. A new application of cell-free bone regeneration: immobilizing stem cells from human exfoliated deciduous teeth conditioned medium onto titanium implants using atmospheric pressure plasma treatment. Stem Cell Res Ther, 2015; 6: 124.
    9. Kawai T, Katagiri W, Osugi M, Sugimura Y, Hibi H, Ueda M. Secretomes from bone marrow derived mesenchymal stromal cells enhance periodontal tissue regeneration. Cytotherapy, 2015; 17: 369-381.
    10. Ogata K, Katagiri W, Osugi M, Kawai T, Sugimura Y, Hibi H, Nakamura S, Ueda M. Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model. Bone, 2015; 74: 95-105.
    11. Matsubara K, Matsushita Y, Sakai K, Kano F, Kondo M, Noda M, Hashimoto N, Imagama S, Ishiguro N, Suzumura A, Ueda M, Furukawa K, Yamamoto A. Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery aftertax spinal cord injury by altering macrophage polarity. J Neurosci, 2015; 35: 2452-2464.
    12. Fujii H, Matsubara K, Sakai K, Ito M, Ohio K, Ueda M, Yamamoto A. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats. Brain Res, 2015; 161: 59-72.
    13. Wakayama H, Hashimoto N, Matsushita Y, Matsubara K, Yamamoto N, Hasegawa Y, Ueda M, Yamamoto A. Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice. Cytotherapy, 2015; 17: 1119-1129.
    14. MatsushitaY, Ishigami M, Matsubara K, Kondo M, Wakayama H, Goto H, Ueda M, Yamamoto A. Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats. J Tissue Eng Regen Med, 2015; 10.1002/term.2086.
    15. Hattori Y, Kim H, Tsuboi N, Yamamoto A, Akiyama S, Shin Y, Katsuno T, Kosugi T, Ueda M, Matsuo S, Maruyama S. Therapeutic Potential of Stem Cells from Human Exfoliated Deciduous Teeth in Models of Acute Kidney Injury. PLoS One, 2015; 10: e0140121.
    16. Fujio M, Xing Z, Sharabi N, Xue Y, Yamamoto A, Hibi H, Ueda M, Fristad I, Mustafa K. Conditioned media from hypoxic-cultured human dental pulp cells promotes bone healing during distraction osteogenesis. J Tissue Eng Regen Med, 2015; 10.1002/term.2109.
    17. Sakakura H, Mii S, Hagiwara S, Kato T, Yamamoto N, Hibi H, Takahashi M, Murakumo Y. CD109 is a component of exosome secreted from cultured cells. Biochem Biophysics Res Commun, 2015; 469: 816-822.
    18. Ichimura N, Shinjo K, An B, Shimizu Y, Yamao K, Ooka F, Katsushima K, Hatanaka A, Tojo M, Yamamoto E, Suzuki H, Ueda M, Kondo Y. Aberrant TET1 methylation closely associated with CpG island methylation phenotype in colorectal cancer. Cancer Prev Res, 2015; 8: 702-711.
    19. Zhang JM, Murakumo Y, Hagiwara S, Jiang P, Mii S, Kalyoncu E, Saito S, Suzuki C, Sakurai Y, Numata Y, Yamamoto T, Takahashi M. CD109 attenuates TGF-beta1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells. Biochem Biophysics Res Commun, 2015; 459: 252-258.
    20. Nagamine K, Hung GC, Li B, Lo SC. DNA sequence signatures for rapid detection of six target bacterial pathogens using PCR assays. Microbiology Insights, 2015; 8: 7-14.
    21. Lo SC, Hung GC, Li B, Lei H, Li T, Nagamine K, Asai S, Zucker MJ, Olesnicky L. Mixed group of Rhizobiales microbes in lung and blood of a patient with fatal pulmonary illness. Int J Clin Exp Pathol, 2015; 8: 13824-13852.
  • 2014年
    1. Sugiyama M, Hattori H, Inoue T, Wakita H, Hibi H, Ueda M. Stem cells from human exfoliated deciduous teeth enhance recovery from focal cerebral ischemia in rats. J Oral Maxillofac Surg Med Pathol, 2014; 26: 443-449.
    2. Ando Y, Matsubara K, Ishikawa J, Fujio M, Shohara R, Hibi H, Ueda M, Yamamoto A. Stem cell-conditioned medium accelerates distraction osteogenesis through multiple regenerative mechanisms. Bone, 2014; 61: 82-90.
    3. Sakakura H,Murakumo Y,Mii S,Hagiwara S,Kato T,Asai M,Hoshino A,Yamamoto N,Sobue S,Ichihara M,Ueda M,Takahashi M.Detection of a soluble from of CD109 transgenic and tumor xenografted mice.PLoS One, 2014; 9: e83385.
    4. Ueda M. A novel approach for skin rejuvenation by regenerative medicine: delivery of stem cell-derived growth factors through an iontophoretic system. Int J Oral Maxillofac Implants, 2014; 29: e59-65.
    5. Yamamoto A, Matsubara K, Kano F, Sakai K. Analysis of the neuroregeneratie activities of mesenchymal stem cells in functional recovery after rat spinal cord injury. Methods in Molecular Biology, 2014; 1213: 321-328.
    6. Yamamoto A, Sakai K, Matsubara K, Kano F, Ueda M. Multifaceted neuro-regenrative activities of human dental pulp stem cells for functional recovery after spinal cord injury. Nerosci, 2014; 78: 16-20.
    7. Hironaka K, Ozaki N, Hattori H, Nagamine K, Nakashima H, Ueda M, Sugiura Y. Involvement of glial activation in trigeminal ganglion in a rat model of lower gingival cancer pain. Nagoya J Med Sci, 2014; 76: 323-332.
    8. Yamano S, Haku K, Yamanaka T, Dai J, Takayama T, Shohara R, Tachi K, Ishioka M, Hanatani S, Karunagaran S, Wada K, Morse AM. The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration. Biomaterials, 2014; 35: 2446-2453.
    9. Uejima S, Fujimoto T, Yokooji M, Mitsudo K, Tohnai I, Ueda M. Synchronous bilateral young cancer treated with chemoradiotherapy using super selective intra-arterial infusion via bilateral superficial temporal arteries: a case report. Head and Neck Oncol, 2014; 18: 42.
  • 2013年
    1. Ikeno M, Hibi H, Kinoshita K, Hattori H, Ueda M. Effects of permeability of shields with autologous bone grafts on bone augmentation. Int J Oral Maxillofac Implants, 2013; 28: e386-e392.
    2. Ikeno M, Hibi H, Kinoshita K, Hattori H, Ueda M. Effects of self-assembling peptide hydrogel scaffold on bone regeneration with recombinant human bone morphogenetic protein-2. Int J Oral Maxillofac Implants, 2013; 28: e283-e289.
    3. Tateishi H, Okamoto Y, Kinoshita K, Hibi H, Ueda M. Effects of implant surface on bone healing around titanium screw implants in ovariectomized rats. Int J Oral Maxillofac Implants, 2013; 28: e252-e259.
    4. Tsuchiya S, Hara K, Ikeno M, Okamoto Y, Hibi H, Ueda M. Rat bone marrow stromal cell-conditioned medium promotes early osseointegration of titanium implants. Int J Oral Maxillofac Implants, 2013; 28: 1360-1369.
    5. Hagiwara S, Yamamoto N, Furue H, Sakakura H, Shigetomi T, Murakumo Y, Hibi H, Takahashi M, Ueda M. Pathological analysis of Ki-67 and CD109 expression in tongue squamous cell carcinoma. J Oral Maxillofac Surg Med Pathol, 2013; 25: 276-287.
    6. Inukai T, Katagiri W, Yoshimi R, Osugi M, Kawai T, Hibi H, Ueda M. Novel application of stem cell-derived factors for periodontal regeneration. Biochem Biophys Res Commun, 2013; 430: 763-768.
    7. Yamada Y, Nakamura S, Ueda M, Ito K. Osteotome technique with injectable tissue-engineered bone and simultaneous implant placement by cell therapy. Clin Oral Implants Res, 2013; 24: 468-474.
    8. Katagiri W, Osugi M, Kawai T, Ueda M. Novel cell- free regeneration of bone using stem cell-derived growth factors. Int J Oral Maxillofac Implants, 2013; 28: 1009-1016.
    9. Tamari M, Nishino Y, Yamamoto N, Ueda M. Acceleration of wound healing with stem cell-derived growth factors. Int J Oral Maxillofac Implants, 2013; 28: e369-375.
    10. Nishiguchi H, Mitsudo K, Yamamoto N, Tohnai, I. Thermochemoradiotherapy using super selective intra-arterial infusion for N3 cervical lymph node metastases of tongue cancer. J Cancer Res Ther, 2013; 9: 718-720.
    11. Yamada Y, Nakamura S, Ueda M, Ito K. Papilla regeneration by injectable stem cell therapy with regenerative medicine: long-term clinical prognosis. J Tissue Eng Regen Med, 2013; 10.1002/term.1737.
    12. Yamagata M, Yamamoto A, Kako E, Kaneko N, Matsubara K, Sakai K, Sawamoto K, Ueda M. Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke, 2013; 44: 551-554.
    13. Hagiwara S, Yamamoto N, Furue H, Sakakura H, Shigetomi T, Murakumo Y, Hibi H, Takahashi H, Ueda M. Pathological analysis of Ki-67 and CD109 expression in tongue squamous cell carcinoma. J Oral Maxillofac Sure Med Pathol, 2013; 25: 276-281.

研究キーワード

組織工学、再生医療、骨再生、培養上清、扁平上皮癌、CD109

大学院医学系研究科博士課程

頭頸部・感覚器外科学講座 顎顔面外科学では学際的に医学博士課程プログラムを展開しており、科学的発見にとどまらず臨床に結びつけることを重要視し、この分野の次世代のリーダーを育成します。