Intervertebral disc regeneration and transcriptional control of nucleus pulpous progenitor cells by in silico pharmacogenesis and iPS technology

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05456
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokai University
• Principal Investigator: SAKAI Daisuke 東海大学, 医学部, 准教授 (10408007)
• Co-Investigator(Kenkyū-buntansha): 檜山 明彦 東海大学, 医学部, 講師 (00514382) ; 平山 令明 東海大学, 先進生命科学研究所, 教授 (70238393) ; 升井 伸治 京都府立医科大学, 医学(系)研究科(研究院), 特任准教授 (20342850)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 椎間板変性 / 再生医療 / 髄核細胞

Outline of Final Research Achievements

Low back pain is considered the major cause of disability worldwide and is linked to a significant socio-economic burden on health care and social security systems. Intervertebral disc disorder is a major cause of low back pain, and a method for artificially deriving intervertebral disc cells has not yet been established. A method for artificially deriving intervertebral disc cells has not been established yet. We set out to search for a method to directly reprogram the intervertebral disc into nucleus pulposus cells. Therefore, we first attempted a comprehensive screening approach to identify transcription factors essential and highly related to the nucleus pulposus cell phenotype. We applied microarray, iPSC interference assay, siRNA assay, gene upregulation assay, and direct cell reprogramming. Combination of 3 strong transcription factors that induces prominent expression of nucleus pulposus cell markers were identified and patented.

Free Research Field

脊椎脊髄病学

Academic Significance and Societal Importance of the Research Achievements

現在、腰痛の新規治療法として、細胞移植を中心とした技術が検討されているが、本研究の結果は椎間板細胞製品のコストダウン、有効性の向上へ寄与できる技術となったほか、未だ発見されていない技術であるため科学的にも意味が大きい研究成果であると考える。