Notch信号通路调控胎肝干/祖细胞治疗终末期肝病的研究进展  

Advances of Notch signaling regulating fetal liver stem/progenitor cells： implications for the therapy of end-stage liver diseases

作　　者：黄启科[1] 尤楠[1] 党立力[1] 刘广欣[1] 陶开山[1] 

机构地区：[1]第四军医大学西京医院肝胆胰脾外科,西安710032

出　　处：《中华肝胆外科杂志》2014年第1期66-69,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金，陕西省科技创新工程重大科技专项课题

摘　　要：细胞治疗是终末期肝病最有前景的疗法.胎肝干/祖细胞（FLSPCs）因高存活、高增殖、小体积和高安全的优势,成为干细胞治疗肝病的理想细胞之一.本课题组前期应用三步分离法富集FLSPCs,获得了与流式分选近似的分离效率,并在大鼠急性肝衰竭模型中证实FLSPCs能参与肝脏形态和功能的恢复.然而,要探索FLSPCs的治疗潜能,有两个问题急待解决：首先,如何保持FLSPCs自我增殖更新;其次,如何促进FLSPCs准确分化为肝细胞和胆管细胞.Notch信号在诸多干细胞更新和分化中起关键调节作用.我们以前的研究显示了Notch信号在肝再生过程中对细胞的增殖和分化有重要作用,Notch信号可能参与FLSPCs的自我更新和定向分化的调控.开展Notch信号对FLSPCs命运的调控效应和相关分子机制研究,发现相应的干预靶点,可能为FLSPCs的临床应用提供依据.Cell therapy has a very promising potential for end-stage liver diseases （ESLD）.Fetal liver stem/progenitor cells （FLSPCs） have advantages of safety,high survival and proliferation rates,and a small volume,all which make them ideal for liver disease stem cell therapy.During the early phase of our study,we applied a three-step separation method to enrich FLSPCs and obtained a separation efficiency similar to that of the flow-cell sorting method.Additionally,using a fulminant hepatic failure model in rats,we have demonstrated that FLSPCs can contribute to morphological and functional recovery of the liver.This manuscript will discuss how FLSPCs can be induced to accurately differentiate into hepatocytes and cholangiocytes and how FLSPCs maintain self-renewal.The Notch signaling plays a critical role in regulating the differentiation and self-renewal of many types of stem cells.Our previous findings have shown that the Notch signaling plays an important role in FLSPCs differentiation into hepatocytes.Therefore,the Notch signaling might be involved in the differentiation and self-renewal of FLSPCs.We conducted a study on the regulatory effects and relative molecular mechanisms of the Notch signaling on FLSPCs and found the corresponding interfering target,which might become an index for the clinical application of FLSPCs.

关 键 词：胎肝干 祖细胞 细胞治疗 终末期肝病 Notch信号通路 Fetal LIVER stem PROGENITOR Cells (FLSPCs) END-STAGE LIVER diseases (ESLDs) 

分 类 号：R575.3[医药卫生—消化系统]