Elucidation of maintenance mechanism of mesenchymal stem cells in keloid to develop new therapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11557
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: Nippon Medical School
• Principal Investigator: Tosa Mamiko 日本医科大学, 医学部, 准教授 (30301568)
• Co-Investigator(Kenkyū-buntansha): 阿部 芳憲 日本医科大学, 先端医学研究所, 助教 (00386153)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: ケロイド / 幹細胞 / ケロイド体質

Outline of Final Research Achievements

Fibroblasts and stem cells were cultured from (1) redness and (2) ridges (3) normal dermis of keloid patients, and (4) dermis-derived fibroblasts and stem cells of healthy individuals without keloid were used as controls. The GLI1 gene was highly expressed in (1), (2), and (3), and when the inhibitor X of the GLI1 gene was allowed to act on the cells, a concentration-dependent inhibitory effect was confirmed only in keloid-derived stem cells. These results suggest that gene A is involved in keloid development and that its inhibitor X may be a new therapeutic agent for keloids. In the future, we will analyze other genes related to GLI1 gene and aim to establish a more effective external drug for keloid treatment with few side effects.

Free Research Field

ケロイド

Academic Significance and Societal Importance of the Research Achievements

Gli1 はヘッジホッグシグナルの標的転写因子である。Gli1 発現は、正常人皮膚では低いのに対して、ケロイド部においては、高発現を認め、興味深いことには、ケロイド患者の正常真皮由来の幹細胞においても高発現を認めたことから、ケロイド発生とケロイド体質決定にGli1 とそれを制御するヘッジホッグシグナルが関与している可能性が非常に高い。研究成果はケロイドの原因解明および新治療の確立につながり、それだけではなく、ケロイド体質診断法の開発創傷治癒メカニズムの解明や癌治療への応用へと発展していく可能性が高く有意義な研究であると考える。