Fabrication of detachable-liver based on liver-derived ECM sponge needle

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19915
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kyushu University
• Principal Investigator: SAKAI Yusuke 九州大学, 工学研究院, 准教授 (10608904)
• Co-Investigator(Kenkyū-buntansha): 江口 晋 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80404218)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 肝臓 / ECM / 構造タンパク質 / スポンジ / ニードル / 肝再生医療

Outline of Final Research Achievements

A multi-layer agarose sponge needle substrate (MS needle) with a film-like surface was fabricated. The MS needle diffused BSA (molecular weight, 66.5 kDa) and inhibited the diffusion of LDH (molecular weight, 140 kDa), suggesting the inhibition of cellular and humoral immunity. Cultured primary rat hepatocytes in the MS needle maintained a high albumin production capacity compared to conventional culture methods. Gene expression levels of Cps1, Arg1 (urea cycle), Foxo1 (gluconeogenesis), G6pc (glycolysis) were also maintained. When the MS needle was punctured into the liver surface and primary rat hepatocytes were inoculated, hepatocyte spheroids were formed and survived for at least 5 days.

Free Research Field

再生医用工学

Academic Significance and Societal Importance of the Research Achievements

本研究では肝臓に着目し、組織・臓器に穿刺して新たに培養足場を提供するシステムを創出した。移植肝細胞に肝臓（ホスト）から液性因子を拡散供給して組織形成を促すと共に、免疫拒絶や細胞拡散を抑制し得た。また、移植後に完全に除去できる特徴を併せ持つ。腫瘍形成リスクを完全には排除できないiPS細胞等の遺伝子操作により作製した細胞を安全に利用できる可能性を有する。様々な組織・臓器に対して新たな生体内培養環境を増設できる発展性からも、革新的な再生医療の実現に大いに貢献し得る。