2022 Fiscal Year Final Research Report

Development of Functional Regenerative Medicine for Hirschsprung's Disease Using Neural Stem Cell Transplantation

Research Project

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Project/Area Number	19K09103
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Juntendo University
Principal Investigator	Fujiwara Naho 順天堂大学, 医学部, 准教授 (20589543)
Co-Investigator(Kenkyū-buntansha)	宮原克順天堂大学, 大学院医学研究科, 技術員 (00420844) 山高篤行順天堂大学, 医学部, 教授 (40200703) 田中奈々順天堂大学, 医学部, 准教授 (50530656)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	腸管神経系 / Hirschsprungs disease / 再生医療 / 細胞治療 / 幹細胞
Outline of Final Research Achievements	Fetal guts from Sox10-Venus mice were dissected on embryonic day 13.5 and cells were dissociated then cultured to generate neurospheres. These neurospheres, which were co-cultured with either dissociated control or HD gut from Sox10-Venus(-) mice on embryonic day 13.5.9.After 4 days, transplanted enteric neurospheres had undergone abundant neuronal migration and ENS had differentiated in the control gut compared with the HD gut. There were many Tuj1-positive neurites in the control and HD groups except in the colons of the HD group. We have shown that neurite outgrowth and branches in both ganglionic and aganglionic segment of HD are significantly decrease compared with controls. 14. We demonstrated that transplanted ENCC did not differentiate properly in HD colon. These results highlight the importance of the neuronal environment of the recipient gut for the ENS development. These results were presented at international scientific meetings and in English papers.
Free Research Field	小児外科
Academic Significance and Societal Importance of the Research Achievements	根治治療となる細胞移植を模索しているが、レシピエントとなる腸管環境が移植細胞の神経発達には大きな影響を与えることが証明された。さらには、移植する腸管の部位によって移植細胞に与える影響も異なるため、慎重な選択が必要となる。これは、いかに正常もしくは分化機能に長けた移植細胞であろうとも、効果的な生着・分化を促すためには、移植する腸管部位の移植時タイミングの環境を整えることが必須となることがわかった。