2022 Fiscal Year Final Research Report

Establishment of a new technique for engineering of muscular tissue using pulripotent-stem-cell containing gel developed from in-body tissue architecture

Research Project

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Project/Area Number	20K08991
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	Saitama Medical University
Principal Investigator	Suzuki Keisuke 埼玉医科大学, 医学部, 客員講師 (50724887)
Co-Investigator(Kenkyū-buntansha)	古村眞東京大学, 医学部附属病院, 特任教授 (10422289) 中山泰秀東京大学, 医学部附属病院, 客員研究員 (50250262) 疋田温彦東京大学, 医学部附属病院, 特任教授 (60443397) 藤代準東京大学, 医学部附属病院, 教授 (60528438)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	生体内組織形成術 / biosheet / 多能性再生幹細胞含有ゲル / 筋肉再生 / 再生医療
Outline of Final Research Achievements	Biosheets fabricated using in-body tissue architecture are reported to be able to induce regeneration of striated muscle and smooth muscle. The purpose of this study is to develop an injectable gel which contains cells and proteins of biosheets and to induce regeneration of muscular tissue. First, we analyzed cells and proteins in biosheets and detected increase of factors which are related to tissue regeneration such as mesenchymal stem cells (MSCs) and hepatocyte growth factor. Next, cells were isolated from biosheets and were suspended in biodegradable gel. The gel was injected to injured rectus abdominis muscles of mice generated by injection of cardiotoxin. However, accelerated reconstitution of muscular tissue could not be achieved until 14 days after injury. It was suggested that development of gels which have more MSCs or proteins extracted from biosheets are required to achieve engineering of muscular tissue.
Free Research Field	再生医療
Academic Significance and Societal Importance of the Research Achievements	biosheetの細胞を含む多能性再生幹細胞含有ゲルは、本研究ではその筋肉再生効果を実証できなかった。しかし、ゲルの開発過程でbiosheetの細胞やタンパク質を解析し、間葉系幹細胞や肝細胞増殖因子など組織再生に関与する因子の存在を確認した。今後は本研究で得られた知見をもとに、これらの因子を精製し濃度を高めたゲルを作成することで、筋肉再生能を有するゲルの開発を目指している。biosheet由来成分を含むゲルによる筋肉再生が可能となれば、胃食道逆流症や鎖肛術後の便失禁など筋肉の低形成・機能不全を有する小児外科疾患に対し、注入療法による筋肉再生という新しい低侵襲な治療法を提供することが可能となる。