细胞分化和细胞恶化:细胞-细胞间的相互作用

在个体的正常发育和异常分化中,细胞间相互关系起着很重要的作用。间叶细胞影响上皮细胞的分化,真皮决定着表皮的分化,间叶细胞影响内胚层细胞,骨髓基质细胞影响血细胞的生长分化,都说明细胞-细胞的相互作用在正常细胞分化中的影响。细胞间正常平衡关系破坏是导致异常分化或肿瘤发生的原因之一。如多瘤病毒诱发上皮癌要有间质参与,癌变发生中上皮细胞和基质细胞都发生变化,并相互影响,癌侵润和结缔组织的关系,以及一些细胞分泌的生长调节因子影响另一些细胞的分化或恶性转化,都分别进行论述。     

成体干细胞的可塑性:横向分化还是细胞融合?

近年来研究显示成体干细胞(adult stem cells)具有可塑性(plasticity),不仅可以生成它们所在组织的成熟细胞,而且在特定环境下能分化成其他组织类型细胞,这种跨系或跨胚层分化现象称为横向分化或转分化(transdifferentiation)。横向分化已为成体干细胞的研究和临床应用包括组织器官损伤的修复提供了新的思路和应用前景。然而,最近的一些研究进展又引出不同的解释,即成体干细胞的可塑性是由于细胞融合(cellfusion)的结果。在此,就成体干细胞的可塑性、横向分化、细胞融合等方面研究作一综述。     

大鼠卵黄囊的分化及其肿瘤性转化研究

目的研究12d大鼠胚胎脏层卵黄囊(VYS)向多胚层组织分化的潜能和在逆转录病毒感染下的肿瘤性转化特征。方法在不同培养条件、移植位点的条件下,观察VYS体内外分化的改变;另外利用逆转录病毒载体将荧光蛋白基因(GFP)转染12d卵黄囊细胞,对GFP标记的转化细胞进行体内外研究。结果在不同培养条件下,均对体外培养的或体内移植的大鼠卵黄囊向三个胚层分化的进程无特异的导向性。将荧光蛋白标记卵黄囊克隆细胞接种在裸鼠皮下长出了未分化的间质细胞肉瘤。结论12d大鼠胚胎脏层卵黄囊具有向三胚层分化的潜能;逆转录病毒感染导致卵黄囊间质细胞发生肿瘤性转化。     

体细胞起源的人胚胎干细胞

根据治疗性克隆假设,可以通过体细胞核移植技术获得与病人具同样基因型的细胞或组织。这样起源的细胞或组织植回病人将不会引起免疫排斥反应。本研究将5岁、42岁、52岁和60岁4个不同年龄的人体细胞核植入去核的兔卵母细胞中重新启动,发育至囊胚,并分离人胚胎干细胞。研究结果提示,年龄不影响体细胞被重新启动的效率。经过核型分析,同源染色体分析,原位杂交,PCR和免疫组化染色等多种鉴定,ntES细胞具有人染色体。ntES细胞可以长期增殖并保持不分化状态,也可以形成类胚体并分化出包括神经和肌肉在内的多种细胞类型。由类胚体诱导生成的混合细胞群体表达所有三个胚层(外、中、内胚层)细胞类型标记,说明ntES细胞具有分化成所有三个胚层的潜力。因此,从人体细胞核获得的ntES细胞与普通人胚胎干细胞一样具有向多种细胞类型分化的能力。     

东方蝾螈早期原肠胚外胚层细胞的细胞周期与反应能力——Ⅱ.阻断细胞周期后的反应能力

两栖类早期原肠胚外胚层细胞具有广泛的潜能,经不同的诱导刺激能向不同的方向分化,例如经缺钙处理可分化成神经组织,而豚鼠骨髓抽提液则可诱导出中胚层组织。但是,不论是哪种情况,诱导作用的强弱程度,都取决于外胚层细胞在接受诱导时的反应能力。Holtfreter首先发现,外胚层对诱导作用的反应能力随年龄不同而有改变。用轻度细胞解体的方法,庄孝僡证明,     

人骨髓基质细胞输注裸鼠后的体内分布

采用密度梯度离心和差速贴壁法分离培养人骨髓基质细胞.对细胞进行形态观察、表型分析、细胞生长曲线和成骨分化潜能测定.然后将第4代细胞通过尾静脉输注到未经任何处理的裸鼠体内,移植1周和4周后,利用RT-PCR检测人Alu基因在裸鼠不同脏器组织中的表达以判断人源性供体细胞的植入情况.结果表明培养的人骨髓基质细胞为CD34 -CD45-成纤维样细胞,并具有向成骨分化的能力,但第1至第5代人骨髓基质细胞增殖速度无显著性差异(P＞0.05).经尾静脉输注后,人源性供体细胞可在肺、肝、脾、肾、肌肉、心、肠、脑等多种脏器或组织中均有不同程度的分布.     

ABCG2/Bcrp1转运蛋白:侧群干细胞的表型标记与功能调控蛋白

在骨髓、骨骼肌及神经组织均发现侧群干细胞（SPSCs）。ABC转运蛋白ABCG2／Bcrp1基因在不同来源侧群（SP）干细胞均呈高表达,且该基因表达与SP细胞表型密切相关。SP细胞能向不同类型或不同胚层的组织细胞分化,很可能代表了一群更原始的干细胞,且与干细胞可塑性相关。而ABCG2／Bcrp1在造血及神经等组织来源的SP干细胞中的特异表达,使得该转运蛋白成为从不同组织中分选多潜能干细胞的一种新的表型标记。     

骨髓基质细胞的特征及其在细胞和基因治疗中的应用

骨髓基质细胞是一类独特的间质干细胞,可分化为多种非造血系的组织。骨髓基质细胞具有贴壁生长的特性,因而易于在体外分离和扩增;另外骨髓基质细胞可在体内外表达多种治疗性的外湖目的基因。因此,骨髓基质细胞被认为是一种理想的治疗性细胞的基因治疗中的靶细胞。本文对骨髓基质细胞的研究进展及其在细胞和基因治疗中的应用作一综述。     

肌源干细胞可塑性研究进展

目前已证实肌肉中至少存在两种干细胞:肌卫星细胞和肌源干细胞。肌源干细胞被认为是卫星细胞的前体细胞,具有较高的增殖能力、更好的细胞生存能力和更宽的分化能力。肌源干细胞不仅能够分化成血、肌肉、脂肪、骨、软骨、内皮等中胚层细胞,而且也能打破胚层限制分化成外胚层和内胚层细胞。文章对肌源干细胞的分离纯化、鉴定、可塑性及临床应用做一综述。     

F9克隆胚胎癌细胞株在诱导分化过程中H-2抗原及花生凝集素受体的变化

近年来有不少研究工作表明,曾被认为是无能的胚胎癌细胞(EC)株的F9细胞,在维生素A酸(简称RA)的影响下能分化成内胚层细胞或神经样细胞等。分化细胞的纤维蛋白溶酶原激活因子和胶原样蛋白都有显著增加,而且细胞表面的抗原、糖蛋白及植物凝集素受体等随之也发生明显变化。某些抗原(如F9抗原)随着分化会逐渐消失,而另一些抗原(如H-2抗原)又会出现。在细胞分化中植物凝集素受体的变化较为显著,其中最令人感兴趣的是花生凝集素受体(简称PNA     

骨髓来源的间充质干细胞分化能力的鉴定

本文研究了人骨髓来源的间充质干细胞(MSCs)的成骨及成脂分化的潜能.通过加入诱导成骨的诱导剂,人的MSCs出现成骨分化的机箱,通过碱性磷酸酶活性测定,茜素红染色及主要调控基因BMP2和Runx2的表达,确定了MSCs具有成骨分化的潜能.对于成脂分化,通过油红O染色,及主要标志基因PPARγ的表达确定其具有成脂分化的潜能.所以,从骨髓分离的到的MSCs纯度达到标准,并且具有成骨成脂分化的多向潜能,是一种理想的实验模型细胞.     

间充质干细胞体外分化为多巴胺能神经元的研究进展

骨髓间充质干细胞（MSCs）有来源广泛、易于分离培养、不易引起免疫排斥等特点,使其成为细胞治疗和基因治疗的种子细胞,具有广泛的科研和临床应用价值。骨髓MSCs具有多向分化潜能,在特定条件下能诱导分化成神经元甚至是更为特异的多巴胺能神经元,为帕金森病进行细胞移植疗法提供了理想的细胞来源。本文就近年来体外诱导MSCs向多巴胺能神经元定向分化所涉及到的常用诱导因素和诱导方法及途径予以综述。     

间充质干细胞影响肿瘤细胞增殖及其分子机理

间充质干细胞MSCs(mesenchymal stem cells)与肿瘤细胞间的相互作用是近年来肿瘤领域的研究热点之一.MSCs是一种多能干细胞,具有分化为成骨细胞、软骨细胞、脂肪细胞、纤维母细胞或肌肉细胞等多种间充质细胞的能力.MSCs在肿瘤细胞中表现出的归巢和转移能力为其成为潜在的抗肿瘤工具奠定了基础,MSCs转移到肿瘤细胞后参与重塑肿瘤微环境,并对其增殖、侵袭和转移等生物学行为产生重要影响.MSCs重塑肿瘤微环境后对肿瘤细胞的增殖究竟是促进还是抑制,相关文献报道有很大的争议.基于相关研究近况,主要综述骨髓间充质干细胞BMSCs(bone marrow derived mesenchymal stem cells)参与重塑肿瘤微环境对肿瘤细胞增殖的影响,并就已知的分子机理做一简要介绍.     

Mesenchymal stem cells: characteristics and clinical applications

Mesenchymal stem cells (MSCs) are bone marrow populating cells, different from hematopoietic stem cells, which possess an extensive proliferative potential and ability to differentiate into various cell types, including: osteocytes, adipocytes, chondrocytes, myocytes, cardiomyocytes and neurons. MSCs play a key role in the maintenance of bone marrow homeostasis and regulate the maturation of both hematopoietic and non-hematopoietic cells. The cells are characterized by the expression of numerous surface antigens, but none of them appears to be exclusively expressed on MSCs. Apart from bone marrow, MSCs are located in other tissues, like: adipose tissue, peripheral blood, cord blood, liver and fetal tissues. MSCs have been shown to be powerful tools in gene therapies, and can be effectively transduced with viral vectors containing a therapeutic gene, as well as with cDNA for specific proteins, expression of which is desired in a patient. Due to such characteristics, the number of clinical trials based on the use of MSCs increase. These cells have been successfully employed in graft versus host disease (GvHD) treatment, heart regeneration after infarct, cartilage and bone repair, skin wounds healing, neuronal regeneration and many others. Of special importance is their use in the treatment of osteogenesis imperfecta (OI), which appeared to be the only reasonable therapeutic strategy. MSCs seem to represent a future powerful tool in regenerative medicine, therefore they are particularly important in medical research.     

Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Prostate-Like Epithelial Cells In Vivo

Although human umbilical cord mesenchymal stem cells (hUC-MSCs) have been identified as a new source of MSCs for potential application in regenerative medicine, their full potential of differentiation has not been determined. In particular, whether they have the capability to differentiate into epithelial cells of endodermal origin such as the prostate epithelial cells is unknown. Here we report that when hUC-MSCs were combined with rat urogenital sinus stromal cells (rUGSSs) and transplanted into the renal capsule in vivo, they could differentiate into prostate epithelial-like cells that could be verified by prostate epithelial cell-specific markers including the prostate specific antigen. The prostatic glandular structures formed in vivo displayed similar cellular architecture with lumens and branching features as seen for a normal prostate. In addition, the human origin of the hUC-MSCs was confirmed by immunocytochemistry for human nuclear antigen. These findings together indicate that hUC-MSCs have the capability to differentiate into epithelial-like cells that are normally derived from the endoderm, implicating their potential applications in tissue repair and regeneration of many endoderm-derived internal organs.     

Trafficking and differentiation of mesenchymal stem cells

Mesenchymal stem cells (MSCs) are a heterogeneous population of stem/progenitor cells with pluripotent capacity to differentiate into mesodermal and non‐mesodermal cell lineages, including osteocytes, adipocytes, chondrocytes, myocytes, cardiomyocytes, fibroblasts, myofibroblasts, epithelial cells, and neurons. MSCs reside primarily in the bone marrow, but also exist in other sites such as adipose tissue, peripheral blood, cord blood, liver, and fetal tissues. When stimulated by specific signals, these cells can be released from their niche in the bone marrow into circulation and recruited to the target tissues where they undergo in situ differentiation and contribute to tissue regeneration and homeostasis. Several characteristics of MSCs, such as the potential to differentiate into multiple lineages and the ability to be expanded ex vivo while retaining their original lineage differentiation commitment, make these cells very interesting targets for potential therapeutic use in regenerative medicine and tissue engineering. The feasibility for transplantation of primary or engineered MSCs as cell‐based therapy has been demonstrated. In this review, we summarize the current knowledge on the signals that control trafficking and differentiation of MSCs. J. Cell. Biochem. 106: 984–991, 2009. © 2009 Wiley‐Liss, Inc.     

透明质酸在间充质干细胞向软骨细胞分化中的应用

随着组织工程学的发展,利用间充质干细胞(mesenchymal stem cells,MSCs)定向分化为软骨细胞,用于治疗骨性关节炎、关节创伤等因素造成的软骨缺损的研究方兴未艾。透明质酸(hyaluronic acid,HA) 是一种酸性多糖类生物大分子,亦是软骨基质的主要成分之一。由于其优良的生物相容性、可降解等特性,HA已成为优良的天然生物材料,其作为支架材料应用于软骨缺损修复已有一段历史。近年来又发现,HA除作为载体支架材料外,还可作为调节因子应用于MSCs向软骨细胞分化。以下将对近年来利用HA应用于MSCs向软骨细胞分化的研究进行总结,旨在为以MSCs为基础的组织工程化软骨的临床应用奠定基础。     

Mesenchymal stem cells: Molecular characteristics and clinical applications

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues. Their ease of isolation and ex vivo expansion combined with their immunoprivileged nature has made these cells popular candidates for stem cell therapies. These cells have the potential to alter disease pathophysiology through many modalities including cytokine secretion, capacity to differentiate along various lineages, immune modulation and direct cell-cell interaction with diseased tissue. Here we first review basic features of MSC biology including MSC characteristics in culture, homing mechanisms, differentiation capabilities and immune modulation. We then highlight some in vivo and clinical evidence supporting the therapeutic roles of MSCs and their uses in orthopedic, autoimmune, and ischemic disorders.     

A case report: bone marrow mesenchymal stem cells from a Rett syndrome patient are prone to senescence and show a lower degree of apoptosis

Rett syndrome (RTT) is one of the most common genetic diseases responsible for a progressive disabling neurodevelopmental disorder. Mutations in the MeCP2 gene were identified in the great majority of RTT patients. MeCP2 protein binds to methylated DNA and produces changes in chromatin structure. This is a key event in regulation of gene expression. It has been suggested that MeCP2 might be important for neuronal development. Moreover, the frequent occurrence of osteoporosis and scoliosis in RTT patients suggests impaired bone formation and/or remodeling. Mesenchymal stem cells (MSCs) can differentiate as mesodermal cells such as bone, cartilage cells, and adipocytes. MSCs have been shown to possess great somatic plasticity; in fact, they can differentiate as neurons and astrocytes. We studied RTT patients' MSCs because they are progenitors of osteocytes, and it has been suggested that RTT patients' osteogenesis could be impaired. Moreover, MSCs might represent a useful model for the study of neurogenesis. MSCs from RTT patient showed precocious signs of senescence in a comparison with the MSCs of healthy-patient control groups. This was in agreement with the reduced gene-expression in the control of stem cell self-renewal and upregulation of lineage specific genes, such as those involved in osteogenesis and neural development. Control groups enabled us to observe a lower degree of apoptosis in RTT patient cells. This means that aberrant stem/progenitor cells, instead of being eliminated, can survive and become senescent. Our research provides a new insight into RTT syndrome. Senescence phenomena could be involved in triggering RTT syndrome-associated diseases.