Artificial biomarkers for monitoring graft function after organ transplantation

• Project/Area Number: 18K16276
• 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: The University of Tokyo
• Principal Investigator: MIZUNO Naoaki 東京大学, 医科学研究所, 特任研究員 (30815642)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Discontinued (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 臓器再生 / 発生工学 / 臓器移植 / ゲノム編集 / バイオマーカー / 遺伝子改変動物

Outline of Final Research Achievements

In this project, we established a new mice model which monitors organ function after transplantation / regenerative medicine. We knocked-in 2A peptide and suicide gene following endogenous albumin coding sequence. 2A tagged Alb could be quantified by ELISA, so the mutant Alb works as an artificial biomarker that represent the residual recipient's liver function. We could estimate recipients' liver function by minimally invasive blood tests instead of pathological assessments from sacrificed mice. However, the serotype of transgenic/endogenous albumin does not linearly correlate with hepatocyte chimerism. It might be because mutant albumin is less-effectively recycled by the FcRn-mediated manner.

Academic Significance and Societal Importance of the Research Achievements

臓器再生研究においては、もともとの臓器の残存機能と再生臓器の機能を切り分けて評価する手法が必要だが、これまでは実験個体を安楽死処理して病理学的に評価する必要があった。本研究では、元の臓器と再生臓器を個別に評価できる人工バイオマーカーを遺伝子改変により導入したマウスを作成し、血液検査を行うことで連続的に臓器機能の移り変わりを評価可能となることを示した。