Establishment of human bone-marrow microenvironment model using Decellularized bone

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15414
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Iichiroh Onishi 東京医科歯科大学, 東京医科歯科大学病院, 助教 (70750214)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脱細胞化骨 / 骨髄間葉系幹細胞株 / CRISPR library

Outline of Final Research Achievements

We successfully transplant human bone marrow mesenchymal stem cell-line, to decellurized bone using CRISPR library. We identified SRRM4 knock out and SHC4 upregulation as bone protrusion factor.
SHC4 overexpression and SRRM4 knock out improved cell migration, and invasion to decellurized bone. Establishment of complete SRRM4 knock out cell line was difficult, but half knock out cell line protrudes into bone trabeculae.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、CRISPR Activation libraryとKnock Out libraryを導入することでUE7T-9の脱細胞化骨への新規侵入因子として、SHC4遺伝子の過剰発現、SRRM4 KOを同定した。脱細胞化骨に進展する因子を同定したことで、今後新たなin vivoヒト骨髄モデル、疾患モデルの構築を十分に遂行可能と考えており、ヒト造血微小環境の解析、造血メカニズム、間質細胞の遺伝子異常による白血病発症メカニズムなどの解析が、飛躍的に進むものと考える。