Investigation of neural crest stem cell therapy for Hirschsprung's disease

• Project/Area Number: 20592091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Keio University
• Principal Investigator: SHIMOJIMA Naoki Keio University, 医学部, 講師 (30317151)
• Co-Investigator(Kenkyū-buntansha): MORIKAWA Yasuhide 慶應義塾大学, 医学部, 教授 (90124958) ; OKANO Hideyuki 慶應義塾大学, 医学部, 教授 (60160694) ; SHIBATA Shinsuke 慶應義塾大学, 医学部, 助教 (70407089) ; NAGOSHI Narihito 慶應義塾大学, 医学部, (助教) (10383837)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 先天性消化器疾患学 / ヒルシュスプルング病 / 小児外科 / 再生医療 / 神経堤 / 幹細胞移植 / 再生医学

Research Abstract

Hirschsprung's disease and allied diseases are congenital loss or abnormal development of enteric nervous system. We investigated a feasibility of neural crest stem cell transplantation as a novel therapy alternative to surgery. Neural crest stem cells are co-cultured with gut from Hirschsprung's disease model. Survival, migration, and differentiation of transplanted cells were investigated.
To clarify etiologies of these disease, genomic DNA is extracted and mutation analyses were carried out.

Research Products

• [Journal Article] Sox10-Venus mice : a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes. (2010)
  • Author(s): Shibata S, Yasuda A, et al.
  • Journal Title: MolBrain. 3 Pages: 31-31
  • Peer Reviewed
• [Journal Article] Hirschsprung病 (2010)
  • Author(s): 下島直樹、森川康英
  • Journal Title: 小児科診療 73 Suppl. Pages: 644-646
• [Journal Article] ヒルシュスプルング病 (2010)
  • Author(s): 下島直樹、森川康英
  • Journal Title: 小児科診療 Volume: 73 Pages: 644-646
• [Journal Article] Ontogeny and multipotency of neural crest-derived stem cells in mouse bone marrow, dorsal root ganglia, and whisker pad. (2008)
  • Author(s): Nagoshi N, Shibata S, et al.
  • Journal Title: Cell Stem Cell 10 ; 2(4) Pages: 392-403
  • Peer Reviewed
• [Journal Article] Ontogeny and multipotency of neural crest-derived stem cells in mouse bone Marrow, dorsal root ganglia, and whisker pad. (2008)
  • Author(s): Nagoshi N, Shibata S, et al.
  • Journal Title: Cell Stem Cell 10:2(4) Pages: 392-403
  • Peer Reviewed
• [Presentation] Isolation, proliferation, and differentiation of neural crest stem/progenitor cells from human gut in normal and motility disorder patients. (2010)
  • Author(s): Naoki Shimojima, Yasuhide Morikawa, Ryuhei Nishikawa, Shinsuke Shibata, Ryo Hotta, Atsuhiro Arisue, Hirofumi Tomita, Fumika Takasato, Masahiro Mori, Yuki Yamamoto, Yasushi Fuchimoto, Hirotoshi Hasegawa, Ken Hoshino, Narihito Nagoshi, Masaya Nakamura, Yumi Matsuzaki, James H.Okano, Hideyuki Okano
  • Organizer: The 4th Scientific Meeting of the Japan-Hungary Surgical Society
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-11-19
• [Presentation] Isolation, proliferation, and differentiation of neural crest stem/progenitor cells from human gut in normal and motility disorder patients (2010)
  • Author(s): Naoki Shimojima, Yasuhide Morikawa, Ryuhei Nishikawa, Shinsuke Shibata, Ryo Hotta, Atsuhiro Arisue, Hirofumi Tomita, Fumika Takasato, Masahiro Mori, Yuki Yamamoto, Yasushi Fuchimoto, Hirotoshi Hasegawa, Ken Hoshino, Narihito Nagoshi, Masaya Nakamura, Yumi Matsuzaki, James H.Okano, Hideyuki Okano
  • Organizer: 23rd International Symposium on Paediatric Surgical Research.
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2010-09-13
• [Presentation] Isolation, proliferation, and differentiation of neural crest stem/progenitor cells from human gut in normal and motility disorder patients (2010)
  • Author(s): Naoki Shimojima
  • Organizer: 23^<rd> International Symposium on Pediatric Surgical Research
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2010-09-13
• [Presentation] 腸管神経再生治療の実験的検討-胎仔無神経節腸管への神経堤幹細胞移植- (2010)
  • Author(s): 下島直樹
  • Organizer: 第46回 日本周産期・新生児医学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-07-12
• [Presentation] ヒルシュスプルング病および類縁疾患の病態解析と腸管神経再生治療に関する基礎的研究 (2010)
  • Author(s): 下島直樹
  • Organizer: 第47回 日本小児外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-06-17
• [Presentation] Isolation, proliferation, and differentiation of neural crest stem cells from human gut. (2010)
  • Author(s): Naoki Shimojima, Yasuhide Morikawa, Ryuhei Nishikawa, Shinsuke Shibata, Ryo Hotta, Hirofumi Tomita, Fumika Takasato, Masahiro Mori, Yuki Yamamoto, Yasushi Fuchimoto, Ken Hoshino, Narihito Nagoshi, Masaya Nakamura, Yumi Matsuzaki, James H.Okano, Hideyuki Okano
  • Organizer: Pacific Association of Pediatric Surgeons 43rd Annual meeting
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-05-26
• [Presentation] Isolation, proliferation, and differentiation of neural crest stem cells from human gut (2010)
  • Author(s): Naoki Shimojima
  • Organizer: 43rd Annual meeting of Pacific Association of Pediatric Surgery
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-05-26
• [Presentation] ヒルシュスプルング病に対する、ヒト腸管を用いた腸管神経再生治療に関する研究 (2010)
  • Author(s): 下島直樹
  • Organizer: 第110回 日本外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] ヒト腸管を用いた腸管神経再生治療の可能性に関する研究(続報) (2010)
  • Author(s): 下島直樹, 西川竜平, 芝田晋介, 堀田亮, 富田紘史, 高里文香, 森昌玄, 山本裕輝, 渕本康史, 星野健, 名越慈人, 中村雅也, 松崎有未, 岡野ジェイムス洋尚, 岡野栄之, 森川康英
  • Organizer: 第22回 日本小腸移植研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-06
• [Presentation] ヒルシュスプルング病および類縁疾患に対する腸管神経再生治療の可能性に関する研究(第3報) (2010)
  • Author(s): 下島直樹, 森川康英, 西川竜平, 富田紘史, 高里文香, 森昌玄, 山本裕輝, 堀田亮, 渕本康史, 星野健, 名越慈人, 中村雅也, 芝田晋介, 岡野ジェイムス洋尚, 岡野栄之
  • Organizer: 第40回日本小児消化管機能研究会
  • Place of Presentation: 山梨
  • Year and Date: 2010-02-20
• [Presentation] Investigation of novel cell replacement therapy for Hirschsprung's disease. (2009)
  • Author(s): Shimojima N, Morikawa Y, Nishikawa R, Shibata S, Hotta R, Nagoshi N, Fuchimoto Y, Hasegawa H, Hoshino K, Nakamura M, Matsuzaki Y, Okano HJ, Okano H.
  • Organizer: XI International Small Bowel Transplantation Symposium
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2009-09-10
• [Presentation] ヒト腸管を用いた腸管神経再生治療に関する研究 (2009)
  • Author(s): 下島直樹, 西川竜平, 芝田晋介, 堀田亮, 名越慈人, 森昌玄, 山本裕輝, 山田洋平, 渕本康史, 星野健, 長谷川博俊, 中村雅也, 岡野ジェイムス洋尚, 岡野栄之, 森川康英
  • Organizer: 第46回日本小児外科学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-06-03
• [Presentation] Migration, localization, and differentiation of neural crest-derived enteric neural precursor cells in aganglionic gut (2009)
  • Author(s): Shimojima N, Morikawa Y, Nishikawa R, Shibata S, Hotta R, Nagoshi N, Nakamura M, Matsuzaki Y, Okano HJ, Okano H
  • Organizer: 7th Stem cell research symposium
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2009-05-15
• [Presentation] Investigation of neural crest stem cell therapy for Hirschsprung's disease (2009)
  • Author(s): Shimojima N, Shibata S, Hotta R, Nishikawa R, Nagoshi N, Okano HJ, Morikawa Y, Okano H
  • Organizer: 2nd International Symposium Development of the enteric nervous system : cells, signals, and genes
  • Place of Presentation: London, England
  • Year and Date: 2009-02-24
• [Presentation] ヒルシュスプルング病に対する神経堤幹細胞移植治療の可能性に関する研究 (2009)
  • Author(s): 下島直樹, 森川康英, 西川竜平, 森昌玄, 山本裕輝, 山田洋平, 堀田亮, 渕本康史, 星野健, 名越慈人, 中村雅也, 芝田晋介, 岡野ジェームズ洋尚, 岡野栄之
  • Organizer: 第39回日本小児消化管機能研究会
  • Place of Presentation: 幕張
  • Year and Date: 2009-02-21
• [Presentation] ヒルシュスプルング病の神経堤幹細胞移植治療に必要とされるニッチ因子の研究 (2009)
  • Author(s): 西川竜平, 下島直樹, 森川康英, 森昌玄, 山本裕輝, 山田洋平, 堀田亮, 渕本康史, 星野健, 名越慈人, 中村雅也, 芝田晋介, 岡野ジェームズ洋尚, 岡野栄之
  • Organizer: 第39回日本小児消化管機能研究会
  • Place of Presentation: 幕張
  • Year and Date: 2009-02-21
• [Presentation] Migration, localization, and differentiation of neural crest-derived enteric neural precursor cells in aganglionic gut (2009)
  • Author(s): 下島直樹, 森川康英, 西川竜平, 芝田晋介, 堀田亮, 名越慈人, 中村雅也, 松崎有未, 岡野ジェイムス洋尚, 岡野栄之
  • Organizer: 7th Stem cell research symposium
  • Place of Presentation: Tokyo
• [Presentation] Investigation of novel cell replacement therapy for Hirschsprung's disease (2009)
  • Author(s): Shimojima N, Morikawa Y, Nishikawa R, Shibata S, Hotta R, Nagoshi N, Fuchimoto Y, Hasegawa H, Hoshino K, Nakamura M, Matsuzaki Y, Okano HJ, Okano H.
  • Organizer: XI International Small Bowel Transplantation Symposium
  • Place of Presentation: Bologna, Italy
• [Presentation] Investigation of neural crest stem cell therapy for Hirschsprung's disease (2009)
  • Author(s): Shimojima N, Shibata S, Hotta R, Nishikawa R, Nagoshi N, Okano HJ, Morikawa Y, Okano H
  • Organizer: 2nd International Symposium on Development of the Enteric Nervous System
  • Place of Presentation: London, UK
• [Presentation] 神経堤幹細胞移植による腸管神経再生治療の可能性に関する研究 (2009)
  • Author(s): 下島直樹, 西川竜平, 芝田晋介, 堀田亮, 名越慈人, 中村雅也, 松崎有未, 岡野ジェイムズ洋尚, 岡野栄之, 森川康英
  • Organizer: 第21回日本小腸移植研究会
  • Place of Presentation: 仙台
• [Presentation] ヒルシュスプルング病に対する神経堤幹細胞移植治療の可能性に関する研究 (2008)
  • Author(s): 下島直樹, 森川康英, 堀田亮, 芝田晋介, 岡野栄之
  • Organizer: 第45回日本小児外科学会学術集会
  • Place of Presentation: つくば
  • Year and Date: 2008-05-30
• [Presentation] Interstitsal Cells of Cajal and enteric neurons in the hypoganglionosis (2008)
  • Author(s): Shimojima N, Mukai M, Yamada Y, Ohno M, Fuchimoto Y, Hoshino K, Morikawa Y
  • Organizer: Pacific Association of Pediatric Surgeons 41st Annual meeting
  • Place of Presentation: Wyoming, USA
• [Presentation] ヒルシュスプルング病に対する神経堤幹細胞移植治療の可能性に関する研究Investigation of neural crest stem cell therapy for Hirschsprung's disease (2008)
  • Author(s): 下島直樹. 森川康英. 堀田亮. 名越慈人. 芝田晋介. 岡野ジェイムス洋尚. 岡野栄之
  • Organizer: 第31回日本神経学大会
  • Place of Presentation: 東京
• [Presentation] ヒルシュスプルング病に対する細胞移植治療の可能性に関する研究 (2008)
  • Author(s): 下島直樹, 森川康英, 森昌玄, 山本裕輝, 山田洋平, 堀田亮, 渕本康史, 星野健, 名越慈人, 中村雅也, 芝田晋介, 岡野ジェイムズ洋尚, 岡野栄之
  • Organizer: 第35回日本臓器保存生物医学会定期学術集会
  • Place of Presentation: 東京
• [Remarks] ホームページ等
  • URL: http://web.sc.itc.keio.ac.jp/surgery/ps/staff/studies.html