2020 Fiscal Year Final Research Report

Attempt to create a peristaltic functional artificial intestine using human-derived stem cells and decellularization technology

Research Project

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Project/Area Number	18K08600
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	Keio University
Principal Investigator	Takumi Fujimura 慶應義塾大学, 医学部(信濃町), 助教 (80573443)
Co-Investigator(Kenkyū-buntansha)	黄地健仁慶應義塾大学, 医学部(信濃町), 助教 (30803564) 黒田達夫慶應義塾大学, 医学部(信濃町), 教授 (60170130) 芝田晋介慶應義塾大学, 医学部(信濃町), 訪問教授 (70407089)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	腸管運動不全 / 人工腸管 / 歯髄細胞 / 神経堤細胞
Outline of Final Research Achievements	As a new treatment for short bowel syndrome and intestinal dismotility, we aimed to construct a functional artificial small intestinal graft which made by decellularization technology and human dental pulp cells. A rat small intestine scaffold could be prepared by decellularization technology, and the properties of the human dental pulp cells to be transplanted could be confirmed. However, in recellarization by transvascular circulation culture (2 weeks), most of the transplanted cells stayed in the mesenterica in the circulation culture route. Immunohistochemistry could not prove the transplanted cells in the intestinal scaffold. Only a few cells could be confirmed by scanning electron microscope. We tried to extend the circulation culture for 4 weeks, but it did not lead to an improvement in the engraftment rate.
Free Research Field	腸管運動不全
Academic Significance and Societal Importance of the Research Achievements	短腸症候群や腸管不全症例に対する根本的治療は小腸・多臓器移植であるが、厳しい免疫抑制を要する治療とドナー不足の問題を抱えている。蠕動しない腸管はうっ滞性腸炎の温床になる危険性を高めるだけであり、これらの問題点を解決するためには自家細胞を用いた免疫抑制を必要としない、蠕動機能を備えた人工臓器の作成を脱細胞技術を用いて作製する必要があると考えた。脱細胞技術を用いる利点は移植時に吻合する血管や腸管内の微細な血管構造を備えており、移植医療に最適と考えたためであるが類洞のようなもともと細胞通過を許容するような構造を備えた肝臓とは異なり、腸管では血管経由以外の再細胞化の方法を検討する必要性が示唆された。