Investigating the wiring mechanisms of nerves and immune cells in the aganglionic segment of Hirschsprung's disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17593
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Juntendo University
• Principal Investigator: Takeda Masahiro 順天堂大学, 医学部, 非常勤講師 (50806164)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ヒルシュスプルング病 / 腸管神経 / 腸管免疫 / 肛門解剖 / anorectal line / 直腸粘膜生検

Outline of Final Research Achievements

This study focuses on the mutual wiring of the nervous and immune systems during development and conducts verifications by: 1) establishing a three-dimensional imaging method through tissue clearing of intestinal tissues in Hirschsprung's disease (HD), 2) morphological observation of M cells in HD, and 3) anatomical verification at the neural terminals of the rectum. It was concluded that the Peyer's patches in HD mice are extremely underdeveloped throughout the period from embryonic stages to 7 days postnatal, making morphological observations difficult. Furthermore, anatomical verification of the enteric nervous system was conducted using human specimens to evaluate the neural endpoints in the anal region. As a result, the anorectal line was confirmed as the baseline for the final endpoints of the intestinal nerves, leading to the establishment of a new rectal mucosal biopsy method.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

本研究により報告した新たな直腸粘膜生検法は、神経系および肛門解剖に基づいた新たな手法である。特に本手法は、ヒルシュスプルング病の病巣である無神経節腸管の肛門側の末端がどこまでかという、病態解明にも直結しており、ヒルシュスプルング病の診断および病態の観点から学術的に有意義な研究成果であったと考えられる。更に病巣の範囲を明確に特定することで、これまで術後合併症として扱われてきた内肛門括約筋アカラジアの存在および解明にも将来的に貢献できると考えられる。また本手法の採用により、これまで世界的にも診断方法が多岐にわたるヒルシュスプルング病において、診断率の向上が期待されることが社会的意義である。