应用小动物活体成像追踪观察EGFP标记的间充质干细胞

为探讨干细胞移植治疗过程中干细胞在体内的存活和迁移能力,利用非细胞损伤性的EGFP(enhanced green fl uorescence protein)标记间充质干细胞进行了实验研究。该研究用电穿孔方法将加强的绿色荧光蛋白表达质粒p CMV-EGFP(cytomegalovirus-EGFP plasmid)转染细胞产生具有EGFP标记的牙髓干细胞、皮肤成纤维细胞(skin fi broblast cells,SFCs)和脐带间充质干细胞。将EGFP标记的脐带间充质干细胞注射到裸鼠皮下,用小动物活体成像系统观察了EGFP标记细胞在体内移植后细胞存活能力和荧光强度随时间的变化情况。结果表明,电穿孔转染能够在体外产生高效表达EGFP的标记细胞,EGFP在牙髓干细胞、SFCs和脐带间充质干细胞中的表达率分别为80%、85%和80%。通过小动物活体成像系统检测表明,EGFP标记的脐带间充质干细胞注射到裸鼠皮下后EGFP荧光表达在7 d后逐渐下降,但免疫组化分析表明,移植细胞可存活6个月以上。该研究提示,EGFP标记的干细胞可用于体内追踪其存活、迁移及分化,为探讨干细胞移植治疗作用提供了实验证据。     

间充质干细胞对免疫细胞的抑制作用及其机制

间充质干细胞是一群来源于发育早期中胚层的具有自我更新和多向分化潜能的干细胞,具有分化为脂肪细胞、肝细胞、成骨细胞、软骨细胞、神经细胞等多种细胞的能力.近年来的相关研究表明,间充质干细胞具有低免疫原性,它可以通过抑制淋巴细胞的增殖、抑制抗原呈递细胞分化成熟及功能发挥、抑制细胞毒性T淋巴细胞的形成、增加调节性T细胞比例等多种途径发挥免疫调节作用,从而成为移植领域、各种退行性和衰竭性疑难病症的替代治疗的研究热点.本文就间充质干细胞对免疫细胞的抑制作用及其机制的研究进展进行综述.     

人间充质干细胞抑制肝癌细胞增殖的作用及其基因表达谱分析

干细胞移植治疗肿瘤具有重要的临床价值．应用人间充质干细胞条件培养液作用H7402肝癌细胞,拟探讨间充质干细胞对肿瘤细胞的抑制作用,为今后应用人间充质干细胞进行肿瘤细胞治疗奠定理论基础．应用胎儿真皮来源的 Z3 间充质干细胞和胎儿骨髓来源的 BMMS-03 间充质干细胞的条件培养液作用于H7402肝癌细胞,采用软琼脂克隆形成实验、流式细胞仪技术、基因芯片技术和免疫印迹技术观察 H7402 细胞的克隆形成、增殖和基因表达谱变化．结果显示,H7402 细胞在间充质干细胞条件培养液作用下,克隆形成和增殖受到了明显抑制;基因芯片检测结果显示,H7402 细胞在间充质干细胞条件培养液作用下有 23 个基因上调表达,17 个基因下调表达,这些差异表达的基因与细胞的转录调控、新陈代谢、信号转导、细胞周期、应激反应和细胞粘附等功能相关．本实验结果表明,人间充质干细胞对 H7402 肝癌细胞的克隆形成和增殖具有抑制作用,并有多种基因的表达发生改变,这些基因表达的改变可能参与了对上述肿瘤细胞的抑制．     

间充质干细胞诱导分化为胰岛β细胞的研究进展

间充质干细胞是一类具有多向分化潜能的成体干细胞,在体内外不仅可以被诱导分化为中胚层细胞,而且可以分化为内胚层和神经外胚层细胞。间充质干细胞易分离,体外可大量扩增,异体移植不引起免疫排斥反应,在细胞治疗和组织工程中具有广阔的应用前景。经过适当诱导,间充质干细胞可能成为胰岛β细胞的来源之一。就间充质干细胞的生物学性状和优势,以及诱导分化为胰岛β细胞的技术方法和发展趋势进行了综述。     

菲立磁标记食蟹猴骨髓间充质干细胞的脑内移植示踪研究

中枢神经系统损伤后的再生修复问题一直是神经科学领域关注的重点之一,骨髓间充质干细胞移植治疗拓宽了人类中枢神经系统损伤的治疗前景,而非侵入性的磁共振成像能活体追踪移植细胞,评价移植效果。应用菲立磁标记食蟹猴骨髓来源的间充质干细胞,在脑立体定位仪引导下,自体脑内移植。结果显示,菲立磁标记间充质干细胞的有效率高达90%以上,移植区磁共振影像呈明显的低信号改变。标记的间充质干细胞移植后在脑内存活,并向周围的脑实质内迁移。移植8周后,发现移植细胞通过血管向对侧脑部迁移,但并未发现移植细胞向神经细胞分化。这些结果提示,菲立磁可用于标记、追踪脑内移植的食蟹猴骨髓间充质干细胞,标记的移植细胞可在脑内存活、迁移。     

阿司匹林对骨髓间充质干细胞移植治疗缺血性脑卒中的影响研究进展

阿司匹林是缺血性脑卒中患者急性期治疗药物及卒中再发的二级预防常用药物,骨髓间充质干细胞(BMSCs)移植是治疗缺血性脑血管疾病的新的新兴技术。已证实阿司匹林可抑制骨髓间充质干细胞的增殖及影响骨髓间充质干细胞的分化。本文就阿司匹林对骨髓间充质干细胞移植治疗缺血性脑卒中的影响等进行综述。     

骨髓间充质干细胞移植与肾脏病

骨髓间充质干细胞是目前广受关注的一群成体干细胞,具有取材容易,增殖能力强,生物学特性稳定,可以跨胚层分化,低免疫源性,参与受损组织修复等优点,随着组织工程的兴起和发展以及其自身所特有的生物学特性,人们逐渐认识到将骨髓间充质干细胞作为肾脏病移植治疗的种子细胞具有良好的应用前景。本文就骨髓间充质干细胞的生物学特性及其在肾脏病移植治疗中的进展做一综述。     

骨髓间充质干细胞移植与肾脏病

骨髓间充质干细胞是目前广受关注的一群成体干细胞,具有取材容易,增殖能力强,生物学特性稳定,可以跨胚层分化,低免疫源性,参与受损组织修复等优点,随着组织工程的兴起和发展以及其自身所特有的生物学特性,人们逐渐认识到将骨髓间充质干细胞作为肾脏病移植治疗的种子细胞具有良好的应用前景。本文就骨髓间充质干细胞的生物学特性及其在肾脏病移植治疗中的进展做一综述。     

脐血干细胞向不同体细胞分化的研究进展

脐血干细胞是一种具有多分化潜能的原始细胞,具备自我更新和增殖的能力,并能在特定因素的影响或诱导下,向多种细胞或组织分化。脐血来源的间充质干细胞不但可以分化为骨、脂肪和软骨,还可以转变成带有神经、肝脏及骨骼肌特异标记的细胞,并且具有应用到组织损伤修复、基因治疗载体和造血干细胞共移植等方面的潜力。旨在对于脐血干细胞在一定条件下分化为多种细胞研究进展进行综述。     

间充质干细胞特性与应用前景

间充质干细胞是中胚层发育的早期细胞,具备干细胞的基本特性。在发育的不同阶段和特定环境条件下,间充质干细胞可向骨、软骨、肌肉、神经、血管及血液细胞等多种方向分化。在成体的很多器官和组织中也存在着间充质干细胞,以备修复和再生所用。间充质干细胞易于体外培养,扩增迅速,可以分化为多种细胞,为干细胞生物工程提供了一个很好的种子细胞。在明确间充质干细胞生物学特性和分化的机制后,可在体外和体内将其定向诱导分化为多种细胞。间充质干细胞具有巨大的临床应用价值和科学研究价值。     

From bone marrow to therapeutic applications: different behaviour and genetic/epigenetic stability during mesenchymal stem cell expansion in autologous and foetal bovine sera?

Bone marrow-derived mesenchymal stem cells are a multipotent adult cellular population endowed with broad differentiation potential. Their regeneration capability, ease to undergo gene modifications, and immuno-suppressive capacity makes them optimal tools for tissue engineering, gene- and immuno-therapy. Due to the ever-increasing number of studies on the clinical applications of mesenchymal stem cells in regenerative medicine, these cells have become attractive targets in clinical transplantation. However, the identification and definition of mesenchymal stem cell culture media for their clinical application in cell therapy is currently a matter of strong discussion. Up to now, clinical studies have been conducted with mesenchymal stem cells cultured in foetal calf serum, and the chance of contamination or immunological reaction towards xenogeneic compounds must be taken into consideration. On the other hand, a serum-free medium without the addition of growth factors is not able to expand these cells in vitro; so the evaluation of which is best, among foetal calf serum, human serum (whether autologous or allogeneic) and platelet-rich plasma, is a hot topic urgently needing further research efforts. The need for the establishment of standardized protocols for mesenchymal stem cell preparations, in order not to interfere with their self-renewal and differentiation processes, assuring durable engraftment and long-term therapeutic effects, is evidently crucial. Therefore, the search for optimal culture conditions for the effective clinical-scale production of vast numbers of mesenchymal stem cells for cellular therapy is of paramount importance and the need for a robust passage from basic to translational research is fundamental.     

The role of stem cells in cardiac regeneration

After myocardial infarction, injured cardiomyocytes are replaced by fibrotic tissue promoting the development of heart failure. Cell transplantation has emerged as a potential therapy and stem cells may be an important and powerful cellular source. Embryonic stem cells can differentiate into true cardiomyocytes, making them in principle an unlimited source of transplantable cells for cardiac repair, although immunological and ethical constraints exist. Somatic stem cells are an attractive option to explore for transplantation as they are autologous, but their differentiation potential is more restricted than embryonic stem cells. Currently, the major sources of somatic cells used for basic research and in clinical trials originate from the bone marrow. The differentiation capacity of different populations of bone marrow-derived stem cells into cardiomyocytes has been studied intensively. The results are rather confusing and difficult to compare, since different isolation and identification methods have been used to determine the cell population studied. To date, only mesenchymal stem cells seem to form cardiomyocytes, and only a small percentage of this population will do so in vitro or in vivo. A newly identified cell population isolated from cardiac tissue, called cardiac progenitor cells, holds great potential for cardiac regeneration. Here we discuss the potential of the different cell populations and their usefulness in stem cell based therapy to repair the damaged heart.     

骨髓间充质干细胞在大鼠实验中的移植途径及比较

骨髓间充质干细胞是具有自我更新能力和分化潜能的一类成体干细胞,经过局部微环境的诱导,可在体内外进行扩展,到晚期可分化成为多种细胞系。当组织受损伤时,可迅速到达损伤部位,分化为特异的组织细胞,参与组织修复。骨髓间充质干细胞这种惊人的分化及组织修复能力,为治疗退行性疾病和器官损伤性疾病提供广阔前景,故成为科研热点。国内外相关实验研究多以大鼠为动物模型,而骨髓间充质干细胞如何进入大鼠体内并定植,是实验成功的重要前提。因此如何找到最合适、最安全的移植途径将骨髓间充质干细胞有效地移植进入大鼠疾病模型体内的受损区域,是研究者关心的重点。本文就目前骨髓间充质干细胞在大鼠实验中不同移植途径进行综述,并比较各种途径的优缺点,希望能对临床科研工作提供参考,并期待能有更成熟的移植手段来推动骨髓间充质干细胞实验研究的进展。     

The effects of ageing on proliferation potential, differentiation potential and cell surface characterisation of human mesenchymal stem cells

Mesenchymal stem cells (MSCs) have a great capacity for use in regenerative medicine and other clinical applications. However, one question creating curiosity of their use, is how they are affected by ageing. As we now live within an ageing population, the prevalence of age related disorders is increasing, so it is important to investigate how effectively MSCs from older patients can be expanded and differentiated in vitro before their use in autologous cell transplantation. This paper will look at how ageing effects proliferation potential, differentiation potential and cell surface characterisation of human mesenchymal stem cells.     

调控软骨形成的信号通路及相关因子在骨髓间充质干细胞骨向分化中的作用*

骨髓间充质干细胞是一类具有自我复制和多向分化潜能的成体干细胞,可以通过定向诱导分化为成骨细胞、软骨细胞、脂肪细胞等,是目前骨再生医学和细胞治疗研究最多的理想种子细胞。在骨缺损的修复过程中,骨髓间充质干细胞内成软骨相关基因表达升高进而分化为软骨细胞,后期随着成骨细胞和破骨细胞的形成及血管长入,软骨基质逐步降解并被骨基质所替换。软骨细胞参与了骨缺损前期的修复过程,调控软骨形成的信号通路及相关因子不仅调控骨髓间充质干细胞成软骨细胞分化,同时在成骨细胞分化过程中也发挥着重要的作用。对调控软骨形成的信号通路及相关因子在骨髓间充质干细胞骨向分化中的调控作用和研究现状进行了总结,以期为临床寻找更好的治疗骨缺损的方法提供理论依据和研究方向。     

Adult mesenchymal stem cells: a pluripotent population with multiple applications

Mesenchymal stem cells (MSCs) have been isolated not only from bone marrow, but also from many other tissues such as adipose tissue, skeletal muscle, liver, brain and pancreas. Because MSC were found to have the ability to differentiate into cells of multiple organs and systems such as bone, fat, cartilage, muscle, neurons, hepatocytes and insulin-producing cells, MSCs have generated a great deal of interest for their potential use in regenerative medicine and tissue engineering. Furthermore, given the ease of their isolation and their extensive expansion rate and differentiation potential, mesenchymal stem cells are among the first stem cell types that have a great potential to be introduced in the clinic. Finally, mesenchymal stem cells seem to be not only hypoimmunogenic and thus be suitable for allogeneic transplantation, but they are also able to produce immunosuppression upon transplantation. In this review we summarize the latest research in the use of mesenchymal stem cells in transplantation for generalized diseases, local implantation for local tissue defects, and as a vehicle for genes in gene therapy protocols.     

干细胞向甲状旁腺细胞的分化及在甲状旁腺功能减退中的研究进展

干细胞是一类能够自我复制、自我更新,具有多向分化潜能,能产生多种分化细胞类型的细胞,由于它的自我复制和多向分化潜能,干细胞技术已经被广泛的应用于细胞移植治疗中。甲状旁腺功能减退作为一种内分泌疾病,目前的治疗方案都不能从根本上治疗该疾病。因此应用干细胞来源的甲状旁腺细胞移植治疗甲状旁腺功能减退越来越受到医学界的重视。目前,已有科研团队报道了应用胚胎干细胞（ESCs）、胸腺上皮细胞和扁桃体间充质细胞向甲状旁腺细胞分化及其在甲状旁腺功能减退中的治疗。本文将干细胞向甲状旁腺细胞的分化及在甲状旁腺功能减退治疗中的研究进展进行综述。     

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。