Design of extracellular matrices for mRNA delivery to cell sheet tissues

2023 Fiscal Year Final Research Report

• Project/Area Number: 18KK0415
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Kobayashi Jun 東京女子医科大学, 医学部, 講師 (20385404)
• Project Period (FY): 2019 – 2023
• Keywords: 細胞シート / 血管新生 / フィブロネクチン / mRNA送達

Outline of Final Research Achievements

The purpose of this study was to develop a culture substrate using extracellular matrix for achieving the highly efficient delivery of messenger RNA (mRNA). We designed a fusion protein that contained heparin-binding peptide and fibronectin for tethering with heparin-immobilized nanofiber scaffolds and demonstrated that it could be produced and purified as a genetically modified organism. In addition, hepatocyte sheet tissue that secretes angiogenic factors was produced by mRNA delivery were transplanted in the subcutaneous space of rats. For four weeks, the engraftment of mRNA-transfected hepatocyte sheets was better than that of non-transfected hepatocyte sheets.

Free Research Field

組織工学

Academic Significance and Societal Importance of the Research Achievements

本研究課題で開発したヘパリン結合性フィブロネクチンとmRNA/カチオンコンプレックスをナノファイバーからなるヘパリン固定化薄膜スキャフォールドに結合させ、効率的なmRNA送達による血管新生因子分泌を誘導することにより、移植した肝細胞シート組織を効率的に生着されることが期待される。これまでに不可能であった肝組織の効率的な移植方法につながり、組織再生治療分野における大きなブレークスルーとなる。