Experimental regeneration of human hair follicles using CD200 positive bulge cells

• Project/Area Number: 18390315
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: OHYAMA Manabu Keio University, 医学部, 講師 (10255424)
• Co-Investigator(Kenkyū-buntansha): MASAYUKI Amagai 慶應義塾大学, 医学部, 教授 (90212563) ; ISHIKO Akira 慶應義塾大学, 医学部, 准教授 (10202988) ; SAITO Masataka 慶應義塾大学, 医学部, 助教 (30306774)
• Co-Investigator(Renkei-kenkyūsha): IWASAKI Toshiro 東京農工大学, 大学院共生科学技術研究院, 教授 (50262754)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,130,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,730,000); Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2006: ¥6,300,000 (Direct Cost: ¥6,300,000)
• Keywords: 皮膚生理学 / 再生医学 / 毛嚢 / 皮膚幹細胞 / バルジ / 毛乳頭 / 組織再構成 / 幹細胞

Research Abstract

CD200と呼ばれる細胞表面のタンパクを目印に、ヒトの毛嚢のもととなる幹細胞を多く含んだケラチノサイト(皮膚の細胞)をヒト頭皮から分離・培養した。また、毛嚢を形作るシグナルを送る能力(毛誘導能)を維持したままヒト毛乳頭細胞を培養する技術を開発した。得られたCD200陽性の毛嚢細胞(バルジ細胞)と毛誘導能を有する毛乳頭細胞を組合せて免疫不全マウスの体内に移植し、ヒト毛嚢に類似した構造体を得ることができた。

Research Products

• [Journal Article] Sparing of the bulge area could preserve intact lower portion of hair follicles in a case of tufted folliculitis (2009)
  • Author(s): Miura M, Dekio I, Yamasaki Y, Ohyama M.
  • Journal Title: J Eur Acad Dermatol Venereol 23(1) Pages: 87-89
  • Peer Reviewed
• [Journal Article] 皮膚幹細胞の新知見 (2009)
  • Author(s): 大山 学
  • Journal Title: 日本皮膚科学会雑誌 (印刷中)
  • NAID: 10028279218
• [Journal Article] Sparing of the bulge area could preserve intact lower portion of hair follicles in a case of tufted folliculitis (2009)
  • Author(s): Miura M, Dekio I, Yamasaki Y, Ohyama M
  • Journal Title: J Eur Acad Dermatol Venereol 23 Pages: 87-89
  • Peer Reviewed
• [Journal Article] 毛包幹細胞・毛包再生の最前線 (2008)
  • Author(s): 大山 学
  • Journal Title: Monthly Book Derma 145 Pages: 7-13
• [Journal Article] Sparing of the bulge area could preserve intact lower portion of hair follicles in a case of tufted folliculitis (2008)
  • Author(s): Miura M, et. al.
  • Journal Title: J Eur Acad Dermatol Venereol (In press)
  • Peer Reviewed
• [Journal Article] Advances in the study of stem-cell-enriched hair follicle bulge cells : A review featuring characterization and isolation of human bulge cells (2007)
  • Author(s): Ohyama M
  • Journal Title: Dermaotlogy 214(4) Pages: 342-351
• [Journal Article] Hair follicle bulge : A fascinating reservoir of epithelial stem cells (2007)
  • Author(s): Ohyama M
  • Journal Title: J Dermatol Sci 46(2) Pages: 81-89
  • NAID: 10024115945
  • Peer Reviewed
• [Journal Article] Gene ontology analysis of human hair follicle bulge molecular signature (2007)
  • Author(s): Ohyama M, Vogel JC, Amagai M.
  • Journal Title: J Dermatol Sci 45 Pages: 147-150
  • NAID: 10024115400
  • Peer Reviewed
• [Journal Article] Advances in the study of stem-cell-enriched hair follicle bulge cells: A review featuring characterization and isolation of human bulge cells. (2007)
  • Author(s): Ohyama M
  • Journal Title: Dermaotlogy 214(4) Pages: 342-351
• [Journal Article] ヒト毛嚢再生に向けてのアプローチ (2007)
  • Author(s): 大山 学
  • Journal Title: 医学のあゆみ 223(11,12) Pages: 922-923
• [Journal Article] 1 (2007)
  • Author(s): 大山 学
  • Journal Title: 日本皮膚科学会雑誌 117(13) Pages: 2415-2417
• [Journal Article] Gene ontology analysis of human hair follicle bulge molecular signature. (2007)
  • Author(s): Ohyama M, Vogel JC, Amagai M
  • Journal Title: Journal of Dermatological Science 45(2) Pages: 147-150
  • NAID: 10024115400
• [Journal Article] The Mesenchymal component of hair follicle neogenesis : Background, methods and molecular characterization
  • Author(s): Ohyama M, Zheng Y, Paus R, Stenn, KS
  • Journal Title: Exp Dermatol (in press)
  • Peer Reviewed
• [Journal Article] The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice
  • Author(s): Kiso T, Tanaka S, Saba R, Matsuda S, Shimizu A, Ohyama M, Okano HJ, Shirotori T, Okano H, Saga Y.
  • Journal Title: Proc Natl Acad Sci USA (in press)
  • Peer Reviewed
• [Journal Article] Hair follicle bulge : A fascinating reservoir of epithelial stem cells.
  • Author(s): Ohyama M
  • Journal Title: Journal of Dermatological Science In press
  • NAID: 10024115945
• [Presentation] 新鮮分離ヒト毛乳頭の分子署名の解明-ヒト毛嚢再生に向けてのアプローチ- (2009)
  • Author(s): 大山 学, 小林哲郎, 清水篤, 天谷雅行
  • Organizer: 第8回日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-06
• [Presentation] An attempt to regenerate human dermal papilla with hair inductive capacity using 3D culture. system (2009)
  • Author(s): Ohyama, M
  • Organizer: Forefront of the regenerative medicine, Symposium 2009
  • Place of Presentation: 東京
  • Year and Date: 2009-01-23
• [Presentation] イヌ毛包はヒト毛包幹細胞研究に有用である-バルジ細胞の類似性を中心に- (2008)
  • Author(s): 小林哲郎, 岩崎利郎, 天谷雅行, 大山 学
  • Organizer: 第15回毛髪科学研究会
  • Place of Presentation: 福岡
  • Year and Date: 2008-11-29
• [Presentation] Identification and isolation of highly proliferative canine hair follicle bulge cells, promising candidates for stem cells. (2008)
  • Author(s): Kobayashi T, Shimizu A, Nishifuji K, Amagai M, Iwasaki T Ohyama M
  • Organizer: World Congress of Veterinary Dermatology 2008
  • Place of Presentation: 香港、中国
  • Year and Date: 2008-11-20
• [Presentation] ヒト毛嚢幹細胞研究のマテリアルとしてのイヌ毛嚢の有用性の検討 (2008)
  • Author(s): 大山 学, 小林哲郎, 岩崎利郎, 天谷雅行
  • Organizer: 第15回分子皮膚科学フォーラム
  • Place of Presentation: 京都
  • Year and Date: 2008-11-14
• [Presentation] レーザーキャプチャーマイクロダイセクションを用いたヒト毛嚢バルジ細胞の分子署名の解明と細胞表面マーカーの同定 (2008)
  • Author(s): 大山 学
  • Organizer: 日本顕微鏡学会第52回シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2008-10-18
• [Presentation] Use of canine hair follicle epithelial hair follicle stem cells for the exploration of novel regenerative medicine approaches (2008)
  • Author(s): Ohyama, M
  • Organizer: BCRT/BMBF Workshop, "Exploitation of hair follicle stem cells in skin defect healing"
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-06-19
• [Presentation] Use of canine hair follicle epithelial hair follicle stem cellsfor the exploration of novel regenerative medicine approaches (2008)
  • Author(s): Ohyama M
  • Organizer: BCRT/BMBF Workshop, “Exploitation of hair follicle stem cells in skin defect healing"
  • Place of Presentation: ベルリン、ドイツ
  • Year and Date: 2008-06-19
• [Presentation] Identification of human bulge cell counterpart in canine hair follicles : A valuable model for stem cell in vesitgation (2008)
  • Author(s): Kobayashi T, Shimizu A, Amagai M, Iwasaki T, Ohyama M.
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-05-17
• [Presentation] Identification of human bulge cell counterpart in canine hair follicles : A valuable model for stem cell investigation. (2008)
  • Author(s): Kobayashi T, Shimizu A, Amagai M, Iwasaki T, Ohyama M
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: 京都
  • Year and Date: 2008-05-17
• [Presentation] Microarray analysis of freshly-microdissected intact human dermal papilla identified upregulation of genes that could contribute to biological distinctiveness (2008)
  • Author(s): Ohyama M, Shimizu A, Kobayashi T and Amagai M.
  • Organizer: International Investigative Deramtology 2008
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2008-05-16
• [Presentation] Microarray analysis of freshly-microdissected intact human dermal papilla identified upregulation of genes that could contribute to biological distinctiveness. (2008)
  • Author(s): Ohyama M, Shimizu A, Kobayashi T Amagai M
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: 京都
  • Year and Date: 2008-05-16
• [Presentation] "Dissecting out molecular signatures of hair follicle key components : Implication of human hair follicle regeneration" Satellite Symposium on Hair Research (2008)
  • Author(s): Ohyama M.
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-05-13
• [Presentation] Dissecting out molecular signatures of hair follicle key components : Implication of human hair follicle regeneration (2008)
  • Author(s): Ohyama M
  • Organizer: Satellite Symposium on Hair Research, International Investigative Dermatology 2008
  • Place of Presentation: 京都
  • Year and Date: 2008-05-13
• [Presentation] 遺伝子発現プロファイルとコロニー形成能からみたヒト毛包バルジ細胞の幹細胞としての特性 (2008)
  • Author(s): 大山 学
  • Organizer: 第7回日本再生医療学会総会シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-13
• [Presentation] ヒト毛乳頭のmolecular signatureの解析-毛乳頭細胞の何が特別なのか?- (2007)
  • Author(s): 大山学、清水篤、天谷雅行
  • Organizer: 第14回分子皮膚科学フォーラム
  • Place of Presentation: 松山
  • Year and Date: 2007-09-15
• [Presentation] ヒト毛乳頭のmolecular signatureの解析-毛乳頭細胞の何が特別なのか (2007)
  • Author(s): 大山 学, 他2名
  • Organizer: 日本研究皮膚科学会第31回年次学術大会
  • Place of Presentation: 松山
  • Year and Date: 2007-09-15
• [Presentation] ヒト毛嚢バルジは幹細胞のニッシェである-Gene Ontoogyによるマイクロアレイデータのバイオインフォーマティックス解析- (2007)
  • Author(s): 大山 学, 他2名
  • Organizer: 日本研究皮膚科学会第31回年次学術大会
  • Place of Presentation: 東京
  • Year and Date: 2007-08-03
• [Presentation] Skin gene therapy: systemic delivery of the anti-hypertensive atrial natriuretic peptide (ANP) by genetically-modified human skin equivalents (HSE) (2007)
  • Author(s): Therrien JP, et. al.
  • Organizer: 日本研究皮膚科学会第31回年次学術大会
  • Place of Presentation: 米国、ロサンゼルス
  • Year and Date: 2007-05-10
• [Presentation] ケラチノサイトの幹細胞 (2007)
  • Author(s): 大山 学
  • Organizer: 第106回日本皮膚科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-04-22
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/derma/r_research/project4.html
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/derma/r_researeh/project4.html
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/derma/r_research/project4.html
• [Patent(Industrial Property Rights)] 特許権 (2008)
  • Inventor(s): 大山学、天谷雅行
  • Industrial Property Rights Holder: 学校法人慶應義塾
  • Filing Date: 2008-08-22
• [Patent(Industrial Property Rights)] 特許権 (2008)
  • Inventor(s): 大山 学, 天谷雅行
  • Industrial Property Rights Holder: 慶應義塾
  • Filing Date: 2008-08-22