基于Wnt/β-catenin信号通路探讨脂肪间充质干细胞移植对泡球蚴感染介导肝再生的机制研究
批准号:
32060223
项目类别:
地区科学基金项目
资助金额:
33.0 万元
负责人:
毕晓娟
依托单位:
学科分类:
组织再生与人工器官
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
毕晓娟
中文摘要
泡球蚴寄生所致肝泡型包虫病(AE)是一种浸润性生长的致死性肝病,俗称虫癌,危害严重,新疆是高发区,患者因余肝不足而无法实施自体肝移植手术。我们前期研究发现泡球蚴感染小鼠移植外源脂肪间充质干细胞可在病灶周围聚集并分化为肝细胞,Wnt高表达,据此提出本课题科学假说“活化Wnt/β-catenin信号通路,促进脂肪间充质干细胞移植修复泡球蚴感染所致肝损伤”。本课题拟采用谱系追踪、脂肪间充质干细胞移植等方法,①研究泡球蚴蛋白对脂肪间充质干细胞向肝细胞样细胞诱导分化能力和募集作用;②明确脂肪间充质干细胞移植对泡球蚴感染所致肝损伤的修复作用、效能、定位、转分化能力及其作用机制;③阐明Wnt/β-catenin信号通路在脂肪间充质干细胞移植修复泡球蚴感染所致肝损伤中的作用及其分子机制,研究结果将极大地丰富脂肪间充质干细胞移植在包虫寄生所致肝损伤中的作用及其机制,为研发新的包虫病临床治疗技术奠定基础。
英文摘要
Hepatic alveolar echinococcosis (AE) caused by alveolar hydatid parasites is an infiltrative and lethal liver disease, commonly known as cancer, which is a serious hazard in Xinjiang, The patient was unable to perform autologous liver transplantation due to insufficient liver . Our previous research found that adipose-derived mesenchymal stem cells can aggregate around the lesion and differentiate into hepatocytes by transplanted in mice infected with Alveolar hydatid, with high expression of Wnt. According to this, the scientific hypothesis of this topic is "Activation of Wnt/β-catenin signaling pathway can promote transplanted adipose-derived mesenchymal stem cells to repair liver damage caused by alveolar cyst infection ". This project intends to use lineage tracking, adipose-derived mesenchymal stem cell transplantation and other methods. ① To study the effect of alveolar hydatid protein on the recruitment and differentiation into hepatocyte-like cells of adipose-derived mesenchymal stem cells ; ②To clarify the repairing effect, efficacy, localization, transdifferentiation ability and mechanism of adipose mesenchymal stem cell transplantation on liver injury caused by alveolar cyst; ③ To elucidate the role and molecular mechanism of Wnt / β-catenin signaling pathway in adipose-derived mesenchymal stem cell transplantation to repair liver damage caused by alveolar cyst infection, the research results will greatly enrich the role and mechanism of adipose-derived mesenchymal stem cell transplantation in liver injury caused by echinococcosis, and lay the foundation for the development of new clinical treatment techniques for echinococcosis.
泡球蚴寄生所致肝泡型包虫病(AE)是一种浸润性生长的致死性肝病,俗称虫癌,危害严重,新疆是高发区,患者因余肝不足而无法实施自体肝移植手术。我们前期研究发现,泡球蚴感染小鼠注射外源间充质干细胞能够减轻肝损伤,肝脏病灶周围有Nestin+间充质干细胞可分化为肝细胞并大量聚集,Wnt5a 在病灶周围组织中高表达,提示间充质干细胞以及Wnt/β-catenin信号通路参与修复泡球蚴感染所致肝损伤。本研究围绕“活化Wnt/β-catenin信号通路,促进脂肪间充质干细胞移植修复泡球蚴感染所致肝损伤”的这一科学问题展开。通过泡球蚴感染小鼠模型和体外细胞实验,发现在E.multilocularis感染中期给予小鼠尾静脉注射ADSCs及诱导的ihep细胞移植后,ADSCs及ihep移植组促进肝细胞增殖、病灶周血管新生,降低肝纤维化。E.m感染小鼠细胞移植ADSCs后,肝脏中Wnt信号通路级联蛋白β-catenin表达水平上调,说明干细胞移植后显著激活了Wnt信号通路。体外构建Wnt缺失脂肪间充质干细胞模型,发现当Wnt5a被抑制后,肝细胞增殖能力降低,RT-qPCR检测发现肝细胞转染慢病毒Wnt5a抑制剂后Wnt/β-catenin信号通路和Nestin表达均被抑制。研究极大地丰富脂肪间充质干细胞移植在包虫寄生所致肝损伤中的作用及其机制,为研发新的包虫病临床治疗技术奠定基础。
国内基金
海外基金