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

• 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: ¥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。

Research Products

• [Journal Article] Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers (2021)
  • Author(s): Ichinohe Norihisa、Ishii Masayuki、Tanimizu Naoki、Mizuguchi Toru、Yoshioka Yusuke、Ochiya Takahiro、Suzuki Hiromu、Mitaka Toshihiro
  • Journal Title: Stem Cell Research & Therapy Volume: 12 Issue: 1 Pages: 312-331
  • DOI: 10.1186/s13287-021-02387-6
  • Peer Reviewed / Open Access