CAJ | 학술논문

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.
세포치료시종말기간병최유전경적요법.태간간/조세포(FLSPCs)인고존활、고증식、소체적화고안전적우세,성위간세포치료간병적이상세포지일.본과제조전기응용삼보분리법부집FLSPCs,획득료여류식분선근사적분리효솔,병재대서급성간쇠갈모형중증실FLSPCs능삼여간장형태화공능적회복.연이,요탐색FLSPCs적치료잠능,유량개문제급대해결:수선,여하보지FLSPCs자아증식경신;기차,여하촉진FLSPCs준학분화위간세포화담관세포.Notch신호재제다간세포경신화분화중기관건조절작용.아문이전적연구현시료Notch신호재간재생과정중대세포적증식화분화유중요작용,Notch신호가능삼여FLSPCs적자아경신화정향분화적조공.개전Notch신호대FLSPCs명운적조공효응화상관분자궤제연구,발현상응적간예파점,가능위FLSPCs적림상응용제공의거.
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.