Research to establish an in vivo plant for clinical application of liver regeneration and replacement therapy.

Research Project

Project/Area Number	18K16263
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	Sapporo Medical University
Principal Investigator	ISHII MASAYUKI 札幌医科大学, 医学部, 研究員 (50643201)
Project Period (FY)	2018-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	小型肝細胞 / Laminin / 前駆細胞 / 肝再生
Outline of Final Research Achievements	We reported that progenitor cells corresponding to parental cells of small rat hepatocytes can be passively cultured on Laminin(LN)111 while maintaining self-renewal ability and basic functions as hepatocytes. This study demonstrated the possibility of selectively culturing cells with higher hepatocyte function. We also reported that miR-146a-5p, which is contained in　extracellular vesicles (EVs) secreted by bone marrow mesenchymal cells, activates hepatic progenitor cells originally existing in the recipient and promotes liver regeneration.
Academic Significance and Societal Importance of the Research Achievements	肝再生医療は国内外において開始されているものの、実臨床においては満足いく成果が出ていないのが現状である。ドナー細胞のハンドリングが非常に困難で、増殖能と高次機能の双方を兼ね備える細胞は、研究協力者の研究室で取り扱っている小型肝細胞のみである。今後はより濃密に増殖能の高い肝駆細胞を選択的に増殖させ、効率よく細胞を供給し、薬剤スクリーニングや再生治療に使用可能なドナー細胞の純化法に応用し、安定した肝細胞供給法の開発を目指す。