HMGB1ペプチドによる胆道閉鎖症の新規内科的治療薬に基づいた再生医療の開発

基于使用 HMGB1 肽治疗胆道闭锁的新疗法的再生医学的开发

• 批准号: 22K15920
• 负责人: 福岡 智哉
• 金额: $ 3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K15920/
• 关键词: 胆道閉鎖症; 再生医学; 間葉系幹細胞; HMGB1ペプチド; 再生医療

本研究では、間葉系骨髄幹細胞が胆道閉鎖症の病態に果たす役割を解明するとともに、胆管結紮モデルおよびrhesus rotavirus (RRV) 誘導性胆道閉鎖症モデルマウスを用いて、、骨髄間葉系幹細胞血中動員活性を有するHMGB1 ペプチドによる、間葉系幹細胞を介した肝臓における抗炎症作用および抗線維化作用の有無とその機序を明らかにすることを目的としている。そのために、胆道閉鎖症モデルの導入とHMGB1ペプチド投与による肝臓における抗炎症作用および抗線維化作用の有無の確認を行いつつ、胆道閉鎖症患者の血中および葛西術時と肝移植時の摘出肝における間葉系幹細胞の検出を行うこととしている。胆道閉鎖症モデルの導入とHMGB1ペプチド投与による肝臓における抗炎症作用および抗線維化作用の有無の確認については、動物実験施設へのマウス導入の事務手続きは終了しており、マウスが導入され次第、胆管結紮およびRRV誘導性の胆道閉鎖症モデルマウスの作成を行う予定である。胆道閉鎖症患者の血中および葛西術時と肝移植時の摘出肝における間葉系幹細胞の検出については、当院で葛西術または肝移植を施行した際に採取され、凍結保存・ホルマリン固定されている肝臓はすでに揃っているため、抗体が入手でき次第、免疫染色による間葉系幹細胞の検出を開始する。また、胆道閉鎖症患者の血液検体については、胆道閉鎖症患者6例、非胆道閉鎖症の胆汁うっ滞症患者8例、非肝疾患コントロール患者3例の検体を揃えており、抗体が入手でき次第、Flow Cytometryを用いた血中間葉系幹細胞の解析を行う予定である。

In this study, patients with chronic biliary tract disease were diagnosed by surgical excision, rhesus rotavirus (RRV), biliary tract disease, chronic biliary tract disease, chronic biliary disease. The function of anti-inflammation, anti-inflammatory, anti-line maintenance, anti-inflammatory, anti-inflammatory and anti-inflammatory. Both HMGB1 and biliary tract disease were implanted into the liver, and the anti-inflammatory effect of the liver was significantly increased. The anti-line maintenance effect was significantly improved. In patients with biliary disease, the blood samples of the patients with biliary disease were significantly higher than those of the control group. When the liver was removed during liver transplantation, the liver was removed. Biliary tract disease is involved in the treatment of HMGB1 and liver disease. The anti-inflammatory effect is related to the anti-inflammatory effect. The anti-line maintenance effect is related to the confirmation of the disease, the operation of the equipment, the operation of the operator, the diagnosis and treatment of the biliary tract, the bile duct, the biliary tract, the bile duct, the bile duct In patients with biliary tract disease, the liver was removed during liver transplantation, and the liver was removed during liver transplantation. during liver transplantation, liver transplantation was performed in patients with biliary disease, and in patients with biliary tract disease, the blood samples of patients with biliary tract disease were removed during liver transplantation, and the cells were removed during liver transplantation. in the current hospital, liver transplantation was performed in the same hospital, and the liver was immobilized. Patients with biliary diseases, 6 patients with biliary diseases, 8 patients with non-biliary diseases, 8 patients with biliary stagnation, 3 patients with non-liver diseases, antibodies, antibodies, and Flow Cytometry were used to analyze and predict the disease.