成体干细胞

在胎儿、儿童和成人组织中存在的多潜能干细胞统称成体干细胞.成体干细胞具有自我更新的能力,并且可以分化成与其来源不同的其他组织类型的细胞.一种组织来源的干细胞可分化成各种类型的细胞,即干细胞可塑性.成体干细胞可塑性是成体干细胞应用于临床的基础,但对干细胞可塑性机制的认识学术界仍存在较大的争议,先后有学者提出脱分化、异质细胞群体和细胞融合等学说,但都不能完全解释成体干细胞的可塑性.近年来的研究提示,成体组织中存在多潜能干细胞,我们发现在胚胎发育后的多种组织中都存在一类原始干细胞群体,在体内、外的特殊环境下,这类原始干细胞可分化为不同胚层的组织细胞,我们称其为亚全能干细胞.亚全能干细胞是存在于人体多种组织中的分化潜能介于从人体胚胎干细胞逐渐形成组织多能干细胞的发育过程中的一种原始干细胞亚群.     

多潜能干细胞的研究进展

多潜能干细胞是一类具有向外胚层、中胚层以及内胚层细胞分化的干细胞,从胚胎发育早期分离获得的胚胎干细胞、胚胎生殖细胞到成体组织骨髓、睾丸中获得的干细胞,都具有三胚层分化能力.近年来,研究证实,可以将成体分化细胞经基因操作逆转为多能干细胞.就各种来源多潜能干细胞的特点予以综述,并对细胞间可能存在的关系加以探讨.     

骨髓间充质干细胞与组织修复

干细胞是一类具有自我更新和分化潜能的细胞群体，根据发生的来源，干细胞可被分为两类：胚胎干细胞和成体干细胞。胚胎干细胞和成体干细胞除了来源不同，其最大的区别在于增殖能力和分化潜能的不同。胚胎干细胞可无限增殖，而成体干细胞的增殖能力则有限。骨髓中除含有能分化发育成各种血细胞的造血干细胞之外，     

干细胞移植与消化系统疾病治疗的进展

干细胞是具有自我更新、高度增殖和特异或多向分化潜能的细胞群体[1],即这些细胞既可通过细胞分裂维持自身细胞群的大小,又可进一步分化成为各种不同的组织细胞,从而构成机体各种复杂的组织器官。按照作用不同干细胞分为3类:全能干细胞、多能干细胞及专能干细胞;按照细胞起源的阶段,大致又划分为胚胎干细胞和成体干细胞。胚胎干细胞具有分化的“全能性”,即能分化成为任何类型的组织和器官,而成体干细胞则是某一类组织或某一胚层组织器官的定向分化细胞,如骨髓造血干细胞、骨髓基质干细胞及内皮祖细胞等。干细胞用于人类疾病的治疗是一个全…     

成体干细胞与胚胎干细胞融合转化机制的研究进展

近年来的研究认为一些组织中的成体细胞同样具有多潜能性 ,能够转化为多种细胞作为替代治疗和基因治疗的载体。然而关于细胞转化机制尚有许多疑问。新近研究表明 ,当成体细胞与胚胎干细胞在体外一起培养时 ,胚胎干细胞诱导成体干细胞转化为形似胚胎干细胞的一种新型细胞 ,而且成体干细胞能与胚胎干细胞自发地融合表现出自己的特征 ,在对干细胞分化、增殖及肿瘤细胞增殖的研究方面给予很大启示     

胚胎干细胞的研究进展

一、研究现状胚胎干细胞 (ｅｍｂｒｙｏｎｉｃｓｔｅｍｃｅｌｌ,ＥＳ)是从早期胚胎中发现、能在体外培养的一种高度未分化细胞 ,它具有发育成各种细胞的潜能。主要来源于两种组织 :早期胚胎细胞团分离的ＥＳ细胞和胚胎生殖嵴分离的胚胎生殖细胞 (ｅｍｂｒｙｏｎｉｃｇｅｒｍｃｅｌｌ,ＥＧ) ,两者的形态、标志、体内分化潜能及种系传递功能都相似[1] 。ＥＳ细胞的研究以小鼠拉开序幕 ,扩展至其它动物 ,最终进入人类ＥＳ细胞研究的主题。 1981年Ｅｖａｎｓ等首次在延缓着床的小鼠胚胎中发现了ＥＳ细胞[2 ] ,Ｍａｒｔｉｎ[3] 、Ａｘ ｅｌｅｒｏ…     

涡虫干细胞研究进展

涡虫具有极强的再生能力,其再生潜能归因于体内一类称为"neoblasts"的细胞群,这是成体涡虫体内仅有的一类具有增殖分化潜能的干细胞,即成体未分化细胞。这种细胞在涡虫体内可以发生迁移、增殖和分化,对虫体组织器官损伤的修复或替代具有重要作用。本文就涡虫干细胞方面的研究进展作一简要介绍。     

脐带基质细胞：一种新型的干细胞来源

本文综述了脐带基质细胞的基本性质,与成体和胚胎间充质干细胞的比较,体内外多向分化潜能的研究进展,揭示脐带基质细胞具有介于成体干细胞和胚胎干细胞之间的干细胞活性,是一种新的更好的干细胞来源。     

成体干细胞的横向分化及其可能的机制

传统的观点认为成体组织中的干细胞,只能定向分化为其所在组织中的某个或某些特定的细胞,其发育潜能具有限制性。近年来随着研究的深入,许多研究者对这一观点提出了质疑,认为成体干细胞的分化潜能远比先前认为的更为广泛,并将之称为干细胞的横向分化。本文综述了几种成体干细胞的横向分化及其可能的机制。     

干细胞研究进展

干细胞包括胚胎干细胞与成体干细胞。介绍了近年来诱导胚胎干细胞向多种或某一种组织细胞分化的实验报道 ,并对成体干细胞“可塑性”分化的几个问题进行了讨论     

Biology of human bone marrow stem cells

The bone marrow is constituted of two separate and distinct stem cells. The hematopoietic stem cells (HSC) are responsible for the production and maintenance of all the mature blood cells. The mesenchymal stem cells constituted the bone marrow stroma. In this report we review our current understanding on both stem cell populations. We also discuss the recent unexpected degree of differentiation plasticity that have been reported recently and the impacts these new discoveries may have in stem cell therapy.     

Biology of human bone marrow stem cells

Abstract. The bone marrow is constituted of two separate and distinct stem cells. The hematopoietic stem cells (HSC) are responsible for the production and maintenance of all the mature blood cells. The mesenchymal stem cells constituted the bone marrow stroma. In this report we review our current understanding on both stem cell populations. We also discuss the recent unexpected degree of differentiation plasticity that have been reported recently and the impacts these new discoveries may have in stem cell therapy.     

Combinatorial action of RUNX1 and PU.1 in the regulation of hematopoiesis

The hematopoietic stem cell (HSC) has the potential to differentiate into mature cells with distinct phenotypes and functions. As suggested in recent reports, this plasticity can expand to include nonhematopoietic lineages, and, indeed, the HSC may repopulate liver and muscle tissues, as well. Considering the flexibility in HSC differentiation, these processes are regulated by a relatively small number of factors, some of which are expressed in all lineages, whereas others are activated only in a specific cell type. Combined evidence from many studies suggests that alternative subsets of these factors work in a combinatorial manner to regulate specific promoters for the induction of a specific lineage. RUNX1 and PU.1 have a fundamental role in HSC differentiation in that multifactor complexes are assembled around these proteins leading to tissue-specific and synergistic gene activation. Here we describe the relationship of RUNX1 with PU.1 as a facet of the combinatorial relationships that determine hematopoietic lineage commitment.     

Potential of hematopoietic stem cell therapy in hepatology: a critical review

Adult stem cell plasticity raised expectations regarding novel cellular therapies of regenerative medicine after findings of unexpected plasticity were reported. In this review, reports of hematopoietic stem cells (HSCs) contributing to hepatocytic lineages are critically discussed with reference to rodent and human models. In particular, the role of liver injury and the potential contribution HSCs make to hepatic regeneration in both injury and physiological maintenance is reviewed. The relative contributions of genomic plasticity and cell fusion are studied across different model systems, highlighting possible factors that may explain differences between often conflicting reports. Insights from experimental studies will be described that shed light on the mechanisms underlying the migration, engraftment, and transdifferentiation of HSCs in liver injury. Although it appears that under differing circumstances, macrophage fusion, HSC fusion, and HSC transdifferentiation can all contribute to hepatic epithelial lineages, a much greater understanding of the factors that regulate the long-term efficacy of such cells is needed before this phenomenon can be used clinically.     

Haematopoietic stem cells

Considerable efforts have been made in recent years in determining the composition of the cell types that constitute the human haematopoietic stem cell (HSC) compartment. These studies have emphasized the heterogeneity of the human HSC in terms of proliferative and self-renewal capacities. Recent studies have indicated that CD34 is not the universal marker of all human HSCs. New markers for purifying HSCs have been described. A number of genes that regulate the formation, self-renewal, or differentiation of HSCs has been identified. The elucidation of the molecular phenotype of the HSC has just begun. Finally, an unexpected degree of developmental or differentiation plasticity of HSC has emerged. This review summarizes all the recent advances made in the human HSC field and examines the impacts that these discoveries may have both clinically and in understanding the organization of the human haematopoietic system.     

Stem cell assays: something old, something new, something borrowed

Numerous assays exist that measure the function of stem cells. In this article, we review in detail the history and future of existing stem cell assays. Hematopoietic stem cells (HSCs) are historically the most well studied, but new developments in stem cell research, including the claim of stem cell plasticity, have caused controversies related to technical issues, as well as to semantics. Stem cell research requires proper definitions, and utilization of stem cell assays, especially since research on non-HSCs that lack solid stem cell assays, is rapidly evolving. These emerging fields may benefit from what has been learned from HSC assays: most important, that the true potential of stem cells can only be assessed retrospectively. This also relates to new developments in HSC research, when limiting numbers of in vitro-manipulated stem cells are transplanted. The most conflicting results arise when cells express stem cell characteristics in one assay but not in another. Should we adjust our definition of a stem cell? If so, when do we decide a claim of stem cell activity to be justified? We therefore recommend using multiple stem cell assays, preferably at least one in vivo assay. These assays should measure functionality of the putative stem cell population.     

The bone marrow: a reserve of stem cells able to repair various tissues?

Hematopoietic stem cells (HSC) have been widely used for autologous and allodeneic transplantation during decades, although little was known about their migration, survival, self-renewal and differentiation process. Their sorting by the CD34(+) marker they express at the cell surface in human has been challenged by the recent discovery of HSC in the CD34(-) compartment that may precede CD34(+) HSC in the differentiation process. Until recently, stem cells present in the bone marrow were thought to be specific for hematopoiesis. Some experiments including clinical trials showing the formation of various tissues, muscle, neural cells and hepatocytes for instance, after transplantation of medullar cells, have challenged this dogma. In fact, the proofs of such a transdifferentiation process by HSC are still missing and the observations may result from the differentiation of other mulipotent stem cells present in the bone marrow, such as mesenchymal stem cells and more primitive multipotent adult progenitor cells (MAPC) and side population (SP) cells.     

Asymmetry of stem cell fate and the potential impact of the niche

Asymmetric cell division is a common concept to explain the capability of stem cells to simultaneously produce a continuous output of differentiated cells and to maintain their own population of undifferentiated cells. Whereas for some stem cell systems, an asymmetry in the division process has explicitly been demonstrated, no evidence for such a functional asymmetry has been shown for hematopoietic stem cells (HSC) so far. This raises the question regarding whether asymmetry of cell division is a prerequisite to explain obvious heterogeneity in the cellular fate of HSC. Through the application of a mathematical model based on self-organizing principles, we demonstrate that the assumption of asymmetric stem cell division is not necessary to provide a consistent account for experimentally observed asymmetries in the development of HSC. Our simulation results show that asymmetric cell fate can alternatively be explained by a reversible expression of functional stem cell potentials, controlled by changing cell-cell and cell-microenvironment interactions. The proposed view on stem cell organization is pointing to the potential role of stem cell niches as specific signaling environments, which induce developmental asymmetries and therefore, generate cell fate heterogeneity. The self-organizing concept is fully consistent with the functional definition of tissue stem cells. It naturally includes plasticity phenomena without contradicting a hierarchical appearance of the stem cell population. The concept implies that stem cell fate is only predictable in a probabilistic sense and that retrospective categorization of stem cell potential, based on individual cellular fates, provides an incomplete picture.     

Hematopoietic Stem Cell Aging: Wrinkles In Stem Cell Potential

Hematopoietic stem cells (HSC) continuously replenish the blood and immune systems. Their activity must be sustained throughout life to support optimal immune responses. It has been thought that stem cells may be somewhat protected from age because of their perpetual requirement to replenish the blood, however studies over the past 10 years have revealed dramatic changes in HSC function and phenotype with respect to age. When the number of HSC within murine bone marrow is measured, an increase in concentration and absolute number of HSC within the bone marrow is observed as the animal ages, paralleled with increased homogeneity of stem cell marker expression. Results from transplantation studies demonstrate that although there is a decline in hematopoietic output on a per-cell basis, the increase in number provides sufficient, yet abnormal, blood production throughout the lifespan of the animal. HSC may play a role in immunosenescence through cell-fate decisions leading to an overproduction of myeloid cells and an underproduction of lymphocytes. When examining gene expression of aged HSC, recent studies have highlighted several key factors contributing to increased inflammation, stress response and genomic instability. Here, we will review the general phenotype observed with aging of the hematopoietic system, focusing on the HSC, and compile recent expression profiling efforts that have examined HSC aging. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.