Basic development for reprogramming methods and translation of regenerative medicine in intervertebral disc cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03809
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokai University
• Principal Investigator: Sakai Daisuke 東海大学, 医学部, 准教授 (10408007)
• Co-Investigator(Kenkyū-buntansha): 升井 伸治 山梨大学, 大学院総合研究部, 特任准教授 (20342850)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 椎間板 / 再生医学 / 腰痛

Outline of Final Research Achievements

The process of translating cell transplantation therapy for disc regeneration into clinical application is underway. As for the final year of the project, we investigated the effects of laminin on cultured nucleus pulposus cells to maintain Tie2 expression during mass culture. To maintain the youthfulness of the nucleus pulposus cells in the regenerative medicine products we are developing, we evaluated the effects of iMatrix-511, a purified human recombinant laminin fragment, on nucleus pulposus cells during the culture process. Cells cultured on laminin showed high Col2 expression at the protein level, but specificity was not confirmed at the RNA level. RNA-seq analysis of signaling pathways, including ECM-related pathways, confirmed that Col2 gene expression gradually decreased over time during culture. Additionally, laminin was found to enhance gene expression related to cell proliferation.

Free Research Field

脊椎脊髄病学

Academic Significance and Societal Importance of the Research Achievements

2020年度にはAMED橋渡しpreBに採択され、PMDAとRS戦略相談（安全性・その他原料試薬に関する品質）を完了した。また椎間板組織の採取、収集および原材料の供給システム構築を完了。さらに2023年度AMED橋渡しシーズFの支援の下、新特許技術で製造した最終製品のPMDA対面助言（安全性）を完了し、非臨床試験（有効性、毒性予備試験）、製品の品質を担保する解析を実施中である。このように、社会的意義が高いと判断されている。