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Gene analyses and neural crest stem cell therapy in Hirschsprung's disease and allied disorders.

Research Project

Project/Area Number 24592700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionKeio University

Principal Investigator

SHIMOJIMA Naoki  慶應義塾大学, 医学部, 講師 (30317151)

Co-Investigator(Kenkyū-buntansha) KURODA Tatsuo  慶應義塾大学, 医学部, 教授 (60170130)
SHIBATE Shinsuke  慶應義塾大学, 医学部, 講師 (70407089)
Co-Investigator(Renkei-kenkyūsha) OKANO Hideyuki  慶應義塾大学, 医学部, 教授 (60160694)
KUDO Jun  慶應義塾大学, 医学部, 教授 (80178003)
KOSAKI Kenjiro  慶應義塾大学, 医学部, 教授 (30234743)
FUJIMURA Takumi  慶應義塾大学, 医学部, 助教 (80573443)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腸管神経 / 発生 / 分化 / 幹細胞 / 再生医療 / 神経堤細胞 / ヒルシュスプルング病 / ヒルシュスプルング病類縁疾患 / hypoganglionosis / 腸管グリア / 神経堤幹細胞 / 網羅的遺伝子解析 / 次世代シーケンサー
Outline of Final Research Achievements

A final goal of our project is to establish a cell transplant therapy for Hirschsprung's disease and allied disorders. Understanding the etiology of diseases is very important, so we began with gene analyses using human samples from patients with hypoganglionosis. To date, we identified 2 candidate genes which might be causative genes.
For a better understanding of etiology of hypoganglionosis, populations of ganglion cells and glial cells were analyzed quantitatively. Immunohistochemical staining for enteric nerves and glial cells were performed. Ganglion cells and glial cells were both decreased in number but the ratio of glial cells to ganglion cells was significantly lower in hypoganglionosis. Thus, the result from a disturbed generation of trophic factors by accompanying glial cells might be an etiological factor for the decreased number of ganglion cells in hypoganglionosis.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Migration and differentiation of transplanted enteric neural crest-derived cells in murine model of Hirschsprung's disease.2014

    • Author(s)
      Nishikawa R, Hotta R, Shimojima N, Shibata S, Nagoshi N, Nakamura M, Matsuzaki
    • Journal Title

      Cytotechnology

      Volume: Epub ahead of print Pages: 0-0

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a nationwide survey.2014

    • Author(s)
      Taguchi T, Kobayashi H, Kanamori Y, Segawa O, Yamataka A, Sugiyama M, Iwanaka T, Shimojima N, Kuroda T, Nakazawa A, Oda Y, Miyoshi K, Ieiri S.
    • Journal Title

      Pediatr Surg Int.

      Volume: 30 (8) Issue: 8 Pages: 815-822

    • DOI

      10.1007/s00383-014-3542-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hirschsprung病のモデルいろいろ2014

    • Author(s)
      下島 直樹, 廣部 誠一
    • Journal Title

      小児外科

      Volume: 46 (6) Pages: 605-608

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Hirschsprung病2014

    • Author(s)
      下島 直樹, 広部 誠一, 福澤 龍二
    • Journal Title

      小児科診療

      Volume: 77 Pages: 699-701

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Hirschsprung病2014

    • Author(s)
      下島直樹
    • Journal Title

      小児科診療

      Volume: 増刊号 Pages: 699-701

    • Related Report
      2013 Research-status Report
  • [Presentation] Population of ganglion cells and glial cells in congenital hypoganglionosis2015

    • Author(s)
      Naoki Shimojima, Takako Yoshioka, Kina Miyoshi, Ken-ichi Kohashi, Yoshinao Oda, Tomoaki Taguchi, Hiroshi Matsufuji, Akihide Tanimoto, Atsuko Nakazawa, Tatsuo Kuroda
    • Organizer
      4th International Symposium Development of the enteric nervous system: cells, signals, genes, and therapy
    • Place of Presentation
      Mainport Hotel Rotterdam(Rotterdam, Holland)
    • Year and Date
      2015-04-19 – 2015-04-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Surgical management for hypoganglionosis: Lessons and learned from 10 cases.2013

    • Author(s)
      Shimojima N et al.
    • Organizer
      XIII International Small Bowel Transplant Symposium - ISBTS 2013
    • Place of Presentation
      OXford, U.K.
    • Related Report
      2013 Research-status Report
  • [Presentation] hypoganglionosisに関する病理学的検討2013

    • Author(s)
      下島直樹
    • Organizer
      第43回小児消化管機能研究会
    • Place of Presentation
      久留米
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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