Development of an efficient method for induction of tendon cell by regulation of mechanical stress response

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20940
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Okayama University
• Principal Investigator: Nakamichi Ryo 岡山大学, 大学病院, 研究准教授 (20803167)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 幹細胞 / 機械刺激応答

Outline of Final Research Achievements

We analyzed the effect of mechanical stimulation on tendon differentiation of stem cells, focusing on PIEZO1, a mechanoresponsive calcium ion channel receptor. With a cell stretching culture system for C3H10T1/2 cells, which are mesenchymal stem cells derived from mouse limb buds, we found that osteogenic differentiation was enhanced under high-load conditions and tenogenic differentiation was enhanced under low-load conditions. Examination of the effect of PIEZO1 agonist stimulation with adjustable firmness gels for cells revealed that ostegenic differentiation markers were upregulated under high firmness conditions and tenogenic differentiation markers were upregulated under low firmness conditions.
Second, studies using stem/progenitor cells derived from tendon tissue revealed that the stimulation by PIEZO1 agonists increased the tendency for tenogenic differentiation independent of firmness.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

上記の研究成果から、細胞周囲環境と機械刺激応答シグナルの調整により間葉系幹細胞の分化方向を制御できる可能性が見出された。Tissue engineeringの分野では１つの臓器を作成するために複数の器官を同時に生成することの困難さが問題点の１つとなっているが、本研究により筋骨格系分野において、幹細胞と周囲環境、機械刺激応答シグナル調整を制御することで、複合組織を生成することができる可能性が示唆された。この研究結果は将来的な整形外科領域における再生医療促進のための基盤研究として社会的意義の高いものと考えられる。