Examination of liver fibrosis and hepatocarcinogenesis by using human iPS cell-derived hepatic stellate cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08415
• 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: Tokyo Medical and Dental University
• Principal Investigator: Nakagawa Mina 東京医科歯科大学, 統合教育機構, 准教授 (30401342)
• Co-Investigator(Kenkyū-buntansha): 柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30372444) ; 朝比奈 靖浩 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (00422692)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒトiPS細胞 / 肝星細胞 / M2BPGi / 肝細胞癌 / SVR

Outline of Final Research Achievements

In this study, we have established a co-culture system of iPS-derived hepatic stellate cells (iPS-HSCs) and human hepatocyte organoids originally, and by using these system, the concentration of M2BPGi (WFA-positive M2BP) in the supernatant increased, which revealed that we could apply these system to a chronic inflammation analysis model. A prospective, multicenter and observational study using the database of patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the patients’ survival after a sustained virological response (SVR). M2BPGi at SVR is a potential predictor for patients’ survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancer related and unrelated to HCV, as well as cardiovascular diseases, after viral eradication. Multicentre retrospective cohort studies including our study have suggested no increase in HCC recurrence and improved survival after DAA treatment.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

研究分担者を中心に開発したヒトiPS細胞培養系を用いた肝疾患病態モデルを用いて行う点は独自性に富むものであり、未だ充分明らかとなっていないウイルス駆除後の肝発癌機構の解明、M2BPGiの機能的意義の解析に向けた慢性炎症モデルへの応用可能と考えられている。未だ充分明らかとなっていないウイルス駆除後の肝内および肝外病態におけるリスク因子としてM2BPGiが同定されたことは、効果的なSVR後サーベイランスを可能とし、個別化医療の発展などへの波及効果をもたらす可能性がある。