A study aming an enhanced liver regeneration using liver stem cell transplantation-Comparative analysis between liver epithelial cells and Muse cells-

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Akita University
• Principal Investigator: Yoshioka Masato 秋田大学, 医学系研究科, 教授 (40375275)
• Co-Investigator(Kenkyū-buntansha): 山本 雄造 秋田大学, 医学系研究科, 教授 (70281730) ; 阿部 ゆき 秋田大学, 医学系研究科, 助教 (50813979)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: LEC / Muse細胞 / 幹細胞 / 肝細胞移植 / 肝切除 / 低酸素耐性 / Microarray

Outline of Final Research Achievements

The possibility of using hepatic epithelial cells (LEC) for stem cell transplantation was examined. We investigated the homology between LEC and Muse cells, which are stem cells, but most of the mesenchymal/pluripotency markers were not expressed in LEC. Therefore, LEC was thought to be in different stages of differentiation with Muse cells. However, LEC has very strong potency for hypoxia, indicating its usefulness for transplantation. In order to search for hypoxia-tolerant genes, microarray system was performed. Since LEC could not proliferate caused by repeated cryopreservation and subculturewas, we used HepG2 cells of human well-differentiated hepatocellular carcinoma. Genes of adrenomedullin and arrestin domain containing 4 were extracted. New hypoxia tolerance genes were pointed out.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

低酸素耐性は細胞移植において移植細胞生存のために非常に重要な要素である。また、低酸素耐性が治療抵抗性の肝細胞癌の生存に寄与しているため、低酸素耐性能に関与する遺伝子を見いだすことは、臨床医学において非常に重要な意味を持つ。本研究では低酸素耐性に関与している可能性のあるadrenomedullinとarrestin domain containing 4という遺伝子の存在が浮き彫りになった。低酸素耐性との関連を明らかにすることで、移植細胞への低酸素耐性能の導入や、臨床における低酸素耐性肝細胞癌治療に貢献できると考える。