Establishment of a liver regeneration treatment model based on cell transplantation and development of a new treatment against immune rejection.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagoya University
• Principal Investigator: Ishikawa Tetsuya 名古屋大学, 医学系研究科(保健), 教授 (10288508)
• Co-Investigator(Kenkyū-buntansha): 林 由美 名古屋大学, 医学系研究科(保健), 講師 (30632707) ; 伊藤 弘康 藤田医科大学, 医学部, 教授 (80373075)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝細胞移植 / 持続性肝不全 / 脂肪由来幹細胞

Outline of Final Research Achievements

We investigated liver regeneration and immune rejection following auto and allo hepatocyte transplantation in a HSVtk (TK transgenic mouse)-ganciclovir administration model. After auto hepatocyte transplantation, the liver at recovery was a chimera of donor and recipient hepatocytes, with a wide range of donor hepatocyte ratios, from approximately 20% to 74%. In auto hepatocyte transplantation, we found that two weeks after transplantation, a transient increase in ALT, infiltration of inflammatory cells into the liver, and increased expression of cytokines/chemokines such as TNF-a, IL-1b, and MCP-1 in the liver were followed by recovery. It was suggested that cell contact signals may be involved in this phenomenon. Adipose-derived stem cells were effective in reducing intrahepatic inflammation during allo transplantation.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

急性・慢性肝不全などの難治性肝疾患に対して、iPS細胞由来肝様細胞、肝organoid、肝細胞そのものを用いた肝再生を目的とする細胞移植治療、及び広範な免疫調節作用を有するASC移入により背景肝の炎症制御を目的とする細胞治療など、細胞移植・移入をベースとした治療法が検討されている。このような治療を実現するためには、急性・慢性肝不全などの病態を再現した動物モデルでの基礎的な検討が必須である。本研究では、持続性肝不全の病態を示すHSVtk-GCVモデルにおいて、auto肝細胞移植が肝不全からの回復をもたらすこと、allo肝細胞移植ではASCが炎症軽減に作用することなど細胞治療の有用性を示した。