肝干细胞的研究进展

自从1997年2月22日英国苏格兰罗斯林研究所威尔穆特博士及其同事成功地克隆出名为多利的绵羊以来,全球掀起了一股有关干细胞的热潮。干细胞是一类具有自我更新与增殖分化能力的细胞,能产生表现型与基因型和自己完全相同的子细胞,同时还能分化为祖细胞。笔者就肝干细胞的生物学特性,其和骨髓、肝癌、胰腺、心脏的关系以及临床应用作一综述。     

肝干细胞的研究进展

肝干细胞是成体千细胞的一种，由于其具有强大的增殖能力，并能分化为具有功能的成熟肝细胞，为肝病的细胞治疗和组织工程提供了重要的细胞来源。现就肝干细胞的来源、标志物、诱导与示踪、体外培养与扩增、分化及其与肝细胞癌的关系作一综述。     

肝干细胞的生物学作用

干细胞是具有自我复制能力和多分化功能的一组细胞。近年来 ,除了造血系统、皮肤等再生力强的组织外 ,在神经系统、骨、肝脏等组织也相继发现了干细胞。本文主要对肝干细胞及其生物学作用进行综述。1　肝干细胞肝干细胞首先是由Ｗｉｌｏｓｎ及Ｌｅｄｎｃ在 195 8年提出的。 2 0世纪 80年代中期Ｚａｊｉｃｅｋ提出了“流肝学说” ,并得到认证。该学说认为肝细胞在肝小叶门脉区生成 ,推向中心静脉区域 ,逐渐成熟至凋亡。他们用3Ｈ -胸腺嘧啶标记分裂期细胞 ,被标记的肝细胞从门脉区向中心静脉区域迁移 ,速度 1 4 4μｍ/天 ,历时 2 0 1天。这提…     

肝干细胞研究进展

肝干细胞（ｈｅｐａｔｉｃ ｓｔｅｍ ｃｅｌｌ）是否存在？如果存在，它们位于肝脏的何处？这些问题已激烈地争论了多年。直到最近，在对啮齿类动物模型的研究及对人类肝脏疾病发病机理的细胞生物学研究获得了确凿的证据之后，才初步平息了争论：肝干细胞确实存在；它们多数位于肝脏Ｈｅｒｉｎｇ管内或其邻近的区域，也有部分来源于肝外的骨髓造血干细胞。现将近年来有关动物模型和人类肝干细胞的研究进展作一综述。１ 动物实验研究１．１ 肝干细胞与受损肝脏再生 正常成年肝脏是一个相对静止的器官，但在外科肝叶切除、病毒感染或化学药物…     

骨髓干细胞向肝系细胞分化的研究

干细胞是一类具有无限或较长的自我更新和增殖分化能力的细胞 ,且具不对称分化性 ,其子代可能是基因型、表现型与自身完全相同的细胞 ,也可能是向前分化了的细胞。因其巨大的增殖、分化潜能 ,目前对干细胞的研究已成为一个热点领域 ,生命科学领域的研究者对干细胞的应用寄予厚望。干细胞可分为胚胎干细胞和成体干细胞 ,前者虽然具有更大的增殖、分化潜能 ,但因受来源和伦理因素的限制 ,近几年对成体干细胞的研究较多且成果显著 ,已在生物学特征、多能分化潜能、分化机制、临床应用方面取得较大的突破。骨髓干细胞是研究较多且较深入的一类成…     

骨髓干细胞向肝系细胞定向分化的研究进展

肝脏疾病是临床的常见病多发病,而传统治疗对终末期肝病的疗效是有限的,原位肝移植虽然是有效的治疗手段,但因为供肝短缺,技术复杂而难以普遍推广。所以,迫切地需要其它可选择的治疗方法。目前,干细胞的研究为解决这个问题带来了新的希望。干细胞是一类具有自我增殖能力和多向分化潜能的细胞,按照其来源可以分为胚胎干细胞和成体干细胞。成体干细胞(somatic/adult stem cells)是分布在已分化的特定组织中的未分化的细胞,其来源包括骨髓、血液、角膜、视网膜、牙髓、肝脏、皮肤、胃肠道和胰腺等。研究发现,成体干细胞不仅能生成它来源组织的…     

肝干细胞的存在及其起源

干细胞生物学是人类基因组主这后最有影响力和最有应用前景的生命科学，近年来由于干细胞理论、临床及科研技术的长足发展，在几乎所有的组织中都发现了干细胞。经过多年的研究，特异性肝干细胞的存在已经被广泛接受，本对有关肝干细胞的存在和起源作一综述，并探讨其激活和增殖分化机制及在肝组织修复再生中所起的重要作用。     

人胎肝干细胞体外分离、培养及鉴定

研究人胎肝干细胞体外分离纯化方法，并对其进行初步鉴定及生物学特性分析。采用胶原酶消化、重力沉降及密度梯度离心方法分离人胎肝干细胞，通过免疫细胞化学方法对其进行初步鉴定，以及应用流式细胞仪等对其生长状况进行评估。所获得的原代细胞共传8代，细胞呈小梭形或三角形，体积较小，胞核较大，而胞浆较少；第4代细胞中进入生长期的细胞约占88．2％；免疫细胞化学染色显示细胞胞质中ALB、CK19染色阳性。人胎肝中存在具有肝干细胞特征的细胞，它们可能会成为细胞移植及肝移植良好的细胞资源。     

肝卵圆细胞——肝干细胞研究进展

<正>近年来对干细胞的研究不断深入,人们发现成年肝组织内存在具有干细胞特性的细胞,在特定环境因素作用下可向肝细胞和胆管细胞分化,甚至可向肝癌细胞方向分化,该细胞被称为肝卵圆细胞或肝前体细胞,是具有一定共性的干细胞群体,与其分化的上下游细胞难以区分,本文就     

肝干细胞研究进展

由于供体器官来源缺乏 ,肝移植治疗肝脏终末期疾病的应用受到限制。于是人们设计出了生物人工肝、肝细胞移植作为肝移植的辅助或替代疗法 ,用来治疗某些肝脏代谢性疾病 ,促进急性肝功能衰竭的肝再生 ,或者在患者得到合适供体肝脏之前提供肝功能支持。对于肝细胞移植及生物人工肝 ,原代肝细胞是患者理想供体 ,但其来源同样缺乏。此外 ,原代肝细胞体外培养或体内移植后的增殖及其功能保持情况不甚理想。研究指出发育的胚胎以及成年体内的某些细胞具有肝干细胞的特性 ,能在一定的条件下增殖并分化成为肝细胞或胆管细胞。这些发现具有重要的临床…     

Update on hepatic stem cells

The liver, like most organs in an adult healthy body, maintains a perfect balance between cell gain and cell loss. Though normally proliferatively quiescent, simple hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response to restore liver mass. This restoration of moderate cell loss and 'wear and tear' renewal is largely achieved by hepatocyte self-replication. Furthermore, cell transplant models have shown that hepatocytes can undergo significant clonal expansion. Such observations indicate that hepatocytes are the functional stem cells of the liver. More severe liver injury activates a facultative stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of biliary epithelia within the lobules before these cells differentiate into hepatocytes. A third population of stem cells with hepatic potential resides in the bone marrow; these haematopoietic stem cells can contribute to the albeit low renewal rate of hepatocytes, make a more significant contribution to regeneration, and even completely restore normal function in a murine model of hereditary tyrosinaemia. How these three stem cell populations integrate to achieve a homeostatic balance is not understood. This review focuses on three aspects of liver stem cell biology: 1) the hepatic stem cell candidates; 2) models of cell transplantation into the liver; and 3) the therapeutic potential of hepatic stem cells.     

Update on hepatic stem cells

Abstract: The liver, like most organs in an adult healthy body, maintains a perfect balance between cell gain and cell loss. Though normally proliferatively quiescent, simple hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response to restore liver mass. This restoration of moderate cell loss and ‘wear and tear’ renewal is largely achieved by hepatocyte self‐replication. Furthermore, cell transplant models have shown that hepatocytes can undergo significant clonal expansion. Such observations indicate that hepatocytes are the functional stem cells of the liver. More severe liver injury activates a facultative stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of biliary epithelia within the lobules before these cells differentiate into hepatocytes. A third population of stem cells with hepatic potential resides in the bone marrow; these haematopoietic stem cells can contribute to the albeit low renewal rate of hepatocytes, make a more significant contribution to regeneration, and even completely restore normal function in a murine model of hereditary tyrosinaemia. How these three stem cell populations integrate to achieve a homeostatic balance is not understood. This review focuses on three aspects of liver stem cell biology: 1) the hepatic stem cell candidates; 2) models of cell transplantation into the liver; and 3) the therapeutic potential of hepatic stem cells.     

Reconstruction of hepatic organoid by hepatic stem cells

Recent advances in culture methods, stem cell research, and tissue engineering provide clues for making tissues in vitro that are functionally and structurally similar to hepatic tissues. To reconstruct hepatic organoids, two approaches to establish the methods have been proposed: the use of cells and the combination of cells and a scaffold (called tissue engineering). Recently, the coculture of hepatic cells (mature hepatocytes, small hepatocytes, hepatoblasts) and hepatic nonparenchymal cells has been reported to form hepatic organoids that possess differentiated hepatic functions. On the other hand, hepatocytes in a roller bottle were shown to form specific structures, consisting of biliary epithelial cells, connective tissue, mature hepatocytes, and endothelial cells. In this review, the studies of hepatic tissue formation in vitro will be summarized.     

辅助性T细胞的研究概况及进展

CD4~ Th细胞是机体重要的免疫调节细胞,根据其产生细胞因子的不同分为Th1和Th2亚型,分别参与调节细胞免疫和体液免疫.Th1和Th2可相互调节,影响免疫应答的格局.他们来自共同的前体细胞Th0,在不同的细胞因子、抗原等因素的影响下,可发生Th1与Th2的转换.在生理条件下,机体Th1/Th2细胞的免疫功能处于动态平衡,一旦这种平衡发生偏离,机体就会趋向疾病状态.     

Biology of hepatic cancer stem cells

Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver and is the third most frequent cause of cancer death worldwide. Although advances in HCC detection and treatment have increased the likelihood of a cure at early stages of the disease, HCC remains largely incurable because of late presentation and tumor recurrence. Only 25% of HCC patients are deemed suitable for curative treatment, with the overall survival at just a few months for inoperable patients. Additionally, this disease is particularly difficult to treat because of the high recurrence rate, its chemotherapy-resistant nature and the premalignant nature of surrounding cirrhotic liver disease. In the past few years, compelling evidence has emerged in support of the hierarchic cancer stem cell (CSC)/tumor-initiating cell (T-IC) model for solid tumors, including HCC. Understanding the characteristics and function of CSCs in the liver has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress in liver CSC research with regard to identification, regulation and therapeutic implications will be discussed.     

肝干细胞研究进展

绝大多数肝干细胞的研究集中在胚胎来源肝干细胞或卵圆细胞。最近研究人员从成体肝脏中鉴定并分离出肝祖细胞,这些细胞也有着双向分化潜能并能多次分裂,从而使肝于细胞定义更加复杂。目前,存在于成体的干／祖细胞群的作用尚未明确,关于对干细胞分化和器官发育的过程的理解亦存在分歧。本文重点讨论从不同发育阶段肝组织中分离的或损伤模型反应性产生的多种肝脏来源干细胞或祖细胞群。     

肝干细胞与肝损伤的研究进展

肝脏疾病是影响人类健康的严重疾病,目前尚没有令人满意的治疗措施,肝移植技术由于供体的数量、昂贵的价格等因素使其应用受到限制.近年来,越来越多的研究对干细胞进行了探索,研究表明,肝干细胞在一定条件下可以分化为肝实质细胞,并在肝损伤修复中起重要作用,本文就干细胞在肝脏疾病中的应用研究作一综述.     

Adipose tissue-derived stem cells: hepatic plasticity

Currently, the only effective treatment for end-stage liver disease is liver transplantation. The number of patients on the waiting list increases considerably each year, giving rise to a wide imbalance between supply and demand for healthy livers. Knowledge of stem cells and their possible use have awakened great interest in the field of hepatology, these cells being one of the most promising short-term alternatives. Hepatic stem cell therapy consists of the implantation of healthy cells capable of performing the functions that damaged cells are unable to carry out. Recent observations indicate that several stem cells can differentiate into distinct cell lineages. Hepatic differentiation of adult stem cells from several origins has yielded highly promising results. Adipose tissue in adults contains a reservoir of stem cells that can be induced and differentiated into different types of cells, showing a high degree of plasticity. Because of its abundance and easy access, adipose tissue is a promising source of adult stem cells for hepatic stem cell therapy. The present article reviews the progress made in the differentiation of adult stem cells from adipose tissue into cells with hepatic phenotype. We also discuss the potential application of this technique as a therapy for temporary metabolic support in patients with end-stage liver failure awaiting whole organ transplantation, as a method to support liver function and facilitate regeneration of the native liver in cases of fulminant hepatic failure, and as a treatment in patients with genetic metabolic defects in vital liver functions.     

Recent insights into hepatic cancer stem cells

It has been suggested that the development of hepatocellular carcinoma (HCC) is related to the existence of cancer stem cells (CSCs) or tumor-initiating cells. Although CSCs populations may be recognized by use of stem cell markers and/or their functional capacities, their profiles might be diverse, because of the heterogeneity of HCC among individuals. Recent studies indicate that activation of CSCs is related to dysregulation of crucial molecular signaling pathways able to alter the intrinsic properties of normal stem cells. This short review describes the latest evidence of the presence of CSCs, alteration of several developmental and oncogenic pathways, CSC-related microRNAs, and drug resistance in HCC. This information may aid the development of potential novel therapy targeting CSCs in HCC.