间质干细胞的生物学特性及其与自身免疫病的关系

骨髓间质干细胞 (mesenchymalstemcells ,MSCs)是中胚层起源的原始细胞 ,可分化成间质组织 ,包括骨、软骨、脂肪、肌肉、肌腱和骨髓基质 ,以及最新研究发现的神经组织。MSCs作为干细胞不仅具有自我更新能力、多向分化潜能 ,还具有很强的可塑性[1 ] ,本文综述MSCs的生物学特性、临床应用前景以及与自身免疫病 (autoimmunediseases,AD)的关系。1　间质干细胞的生物学特性MSCs和造血干细胞 (hematopoieticstemcells ,HSC)均主要来自于骨髓 ,但MSCs是一类与HSC截然不同的干细胞。原因如下 :①MSCs不表达造血细胞系的表面标记物 ,如脂…     

缺血性心脏病细胞移植疗法的理想工具--骨髓基质干细胞

骨髓基质干细胞是一种由骨髓中分离获得的具有多种分化潜能的间质干细胞。在体外培养条件下，它可以分化为成骨细胞、软骨细胞、脂肪细胞、甚至于成肌细胞。因为骨髓基质干细胞具有易于获取、分高方便和良好的分化特性等特点，在细胞移植和基因治疗方面具有非常巨大的应用前景。对于缺血性心脏病而言，骨髓基质干细胞是非常好的细胞移植供体，对于改善心功能帮助巨大。本文献骨髓基质干细胞的生物学特性和在缺血性心脏病治疗中的应用前景进行简要综述。     

间质干细胞和自身免疫病

造血干细胞在自身免疫病中的研究是近年来的热点之一。骨髓中除了有造血干细胞之外，还存在间质干细胞(ruesenchymal stem cells，MSCs)，它能够分化成多种中胚层来源的间质细胞。对MSCs的生物学特性己进行了广泛深入的研究，通过组织工程技术体外分离和定向培养所需的靶细胞，用于多种疾病的治疗。但MSCs在自身免疫病如系统性红斑狼疮(systemic lupus erythematosus，SLE)、类风湿关节炎(rheumatoid arthritis．RA)中的研究报道较少。本研究对MSCs的生物学和免疫学特性及在自身免疫病中的研究进行综述。     

骨髓间充质干细胞及其在缺血性脑血管病中的应用

骨髓间充质干细胞是骨髓中的一群非造血干细胞，具有较强的自我更新能力和多向分化潜能，在体外不同诱导条件下可分化为骨细胞、神经细胞和平滑肌细胞等多种细胞。骨髓间充质干细胞已应用于缺血性脑血管病的治疗研究。文章对骨髓间充质干细胞及其在缺血性脑血管病中的应用做了综述。     

自体骨髓间充质干细胞联合造血干细胞共移植治疗恶性血液病五例疗效观察

目的 研究自体骨髓间充质干细胞(MSCs)与造血干细胞共移植治疗恶性血液病的安全性和可行性,及其对移植后造血重建的影响.方法 从无骨髓浸润的恶性血液病患者本人骨髓中分离、培养间充质干细胞,经放化疗等预处理后,与造血干细胞共移植治疗恶性血液病患者5例,其中恶性淋巴瘤4例,粒细胞肉瘤1例,并观察其对移植后造血重建的影响.结果 MSCs联合造血干细胞共移植治疗恶性血液病患者5例,MSCs输注过程顺利,未见明显不良反应.移植后造血恢复过程中,中性粒细胞≥0.5×109/L的中位时间为9.4(8～11)d、血小板≥20×109/L的中位时间为12.2(10～14)d.结论 MSCs联合造血干细胞共移植治疗恶性血液病安全性好,未见明显副作用.结果 提示输注MSCs可促进造血恢复,但其远期疗效仍有待于进一步观察.     

骨髓干细胞移植与缺血性心脏病

近些年来 ,国内外大量动物实验研究及临床应用研究表明 ,骨髓干细胞移植在缺血性心脏病治疗上具有极广阔的前景 ,从而为人类解决缺血性心脏病这一公共卫生问题带来新的希望。本文就骨髓干细胞移植在缺血性心脏病中应用进展作一综述。     

骨髓间充质干细胞及基因治疗心血管疾病的研究进展

骨髓间充质干细胞（mesenchymal stem cells，MSCs）是存在于骨髓中，除造血干细胞外的另一类早期前体细胞；其来自基质，也称骨髓基质干细胞。1987年Friedenstein等在分离大鼠骨髓成骨祖细胞时，首次从骨髓基质中鉴定出一种非造血系成体多能干细胞，并实验证实在体外这类细胞能分化成各种间质细胞，包括成骨细胞、脂肪细胞、软骨细胞和肌肉细胞等，因而称之为MSCs。     

骨髓间质干细胞分化为内皮细胞增加血管密度改善慢性缺血狗的心功能

Silva GV,Litovsky S,Assad JA,et al.Mesenchymal stem cells differentiate into an endothelial phenotype,enhance vasculardensity,and improve heart function in a canine chronic ischemia model.Circulation,2005,111(2):150-156.骨髓来源的干细胞治疗缺血性心脏病正在研究中。骨髓间质干细胞(mesenchymal stem cells,MSCs)一直被用于急性缺血性模型,但缺乏对慢性缺血模型的研究。因此,作者对12只狗安装动脉缩窄器(ameroid constrictor),30日后,在6只狗心肌内注射MSCs(100×106MSCs/10ml生理氯化钠);对照组6只狗仅注射生理…     

PBSCs与MSCs协同移植治疗恶性血液病的研究进展

近30年来,外周血造血干细胞移植（PBSCT）的实验研究与临床应用发展较快。与骨髓移植（BMT）比较,PBSCT后受者造血重建较快、移植物抗白血病（GVL）作用较强、复发率较低,但造血恢复较慢、慢性移植物抗宿主病（GVHD）发生率较高。近年研究表明,人骨髓间充质干细胞（MSCs）是骨髓微环境中的一个主要组分,     

间充质干细胞治疗在肝病中的应用

目的间充质干细胞(MSCs)属于中胚层的多功能干细胞,具有多向分化的潜能。在特定条件下,MSCs可分化为肝细胞、胰岛样细胞、骨细胞、软骨细胞、心肌细胞、平滑肌细胞、肌腱细胞、成纤维细胞、骨髓基质细胞、神经元、神经胶质细胞及造血系统等。因此,MSCs已成为细胞替代治疗中的主要选择细胞,广泛用于多种疾病的细胞治疗。本文就MSCs在肝脏疾病中的应用作一概述。     

祖细胞和干细胞与缺血性疾病的治疗

缺血性疾病是严重危害人类健康的疾病之一,主要包括缺血性脑血管疾病、缺血性心血管疾病、下肢缺血性疾病等。祖细胞和干细胞都是具有自我复制能力的多潜能细胞,在一定条件下,它们可以分化成多种功能细胞。根据干细胞所处的发育阶段分为胚胎干细胞和成体干细胞,虽然胚胎干细胞具有万能分化型功能,但伦理学方面的争议使其研究困难重重,而成体干细胞相较胚胎干细胞,不仅避免了伦理学方面的争议问题,而且无移植后免疫排斥反应。本文主要讨论成体干细胞和祖细胞在缺血性疾病中的应用。近年来,关于祖细胞和干细胞在缺血性疾病中应用的研究日益增多,受到了广泛的关注,为我们提供了一条治疗缺血性疾病的新思路。     

Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy

Current treatments for ischemic cardiomyopathy are aimed toward minimizing the deleterious consequences of diseased myocardium. The possibility of treating heart failure by generating new myocardium and vascular tissue has been an impetus toward recent stem cell research. Mesenchymal stem cells (MSC), also referred to as marrow stromal cells, differentiate into a wide variety of lineages, including myocardial and endothelial cells. The multi–lineage potential of MSCs, their ability to elude detection by the host immune system, and their relative ease of expansion in culture make MSCs a very promising source of stem cells for transplantation. In addition, emerging experimental results with MSCs offer novel mechanistic insights into cardiac regenerative therapy in general. Here we review the characterization of MSCs, animal and human trials studying MSCs in cardiomyogenesis and vasculogenesis in postinfarct myocardium, routes of delivery, and potential mechanisms of stem cell repair.     

MSCs分化为功能性肝细胞的研究进展

间充质干细胞(mesenchymal stemcells,MSCs)来源于中胚层间充质,广泛存在于骨髓、脐带组织、脐血、外周血、脂肪等组织中.在特定条件下,可以分化为骨、脂肪、神经细胞及肝细胞等多种细胞,进而作为一种替代器官移植的新的治疗方法.近年来,肝硬化等终末期肝病的发病率日益上升,成为影响人类健康的重大疾病之一.肝源紧张、免疫排斥限制了肝移植的临床应用,然而众多研究证实MSCs对肝纤维化、肝硬化等肝病的治疗作用可能与其分化为功能性肝细胞有关,但具体机制尚不十分清楚.本文就MSCs的分化能力及其分化的调控、分子机制和不同来源干细胞对肝纤维化的治疗作用作一综述.     

Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart

Myocardial infarction may cause sudden cardiac death and heart failure. Adult cardiac myocytes do not replicate due to lack of a substantive pool of precursor, stem, or reserve cells in an adult heart. Ventricular myocytes following myocardial infarction are replaced by fibrous tissue and this leads to congestive heart failure in severe cases. Anversa et al. described that resident cardiac stem cells are present in the heart, and can repair the damaged mycardium by myocyte regeneration. Recent findings suggest the feasibility of cardiac repair using cell transplantation. However, it remains controversial which cell types are the best for cell transplantation in the ischemic heart. In this study, we demonstrate that cultured bone marrow stromal cells (MSCs) and Lin(-) bone marrow cells upon transplantation differentiate into myocytes and endothelial cells in the ischemic heart, eventually reducing both infarct size and fibrosis.     

Melatonin facilitates adipose‐derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway

Mesenchymal stem cells (MSCs)‐based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose‐derived mesenchymal stem cells (AD‐MSCs)‐based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD‐MSCs in infarcted heart and provoked a synergetic effect with AD‐MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD‐MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti‐apoptotic protein Bcl2, and decreased the expression of Ac‐FoxO1, Ac‐p53, Ac‐NF‐ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD‐MSCs‐based therapy in MI, possibly through promoting survival of AD‐MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC‐based therapy for IHD, possibly through SIRT1 signaling evocation.     

巨噬细胞与间充质干细胞相互作用及其对缺血性心脏病的影响

心肌梗死发生后,缺血及周边区域发生的炎症反应贯穿了心肌组织修复及纤维化的始终。巨噬细胞作为炎症反应的重要组分,在心肌损伤后的修复过程中至关重要。不同亚型的巨噬细胞参与了心肌梗死的各个阶段,并发挥着吞噬凋亡细胞、促进血管新生、促进瘢痕形成等多种作用。移植间充质干细胞也因具有免疫调控、旁分泌心肌保护等多种效应,被广泛用于缺血性心衰的研究中。近年来研究发现,巨噬细胞和间充质干细胞在治疗缺血性心脏病中有着密切联系,间充质干细胞可减少促炎型巨噬细胞在炎症部位的募集,并诱导巨噬细胞由促炎型向抗炎型转化,从而促进心肌修复。而巨噬细胞可影响间充质干细胞的生存、增殖、迁移及免疫调控等功能,从而改变其心肌修复效果。本文就巨噬细胞与间充质干细胞相互影响及其在缺血性心脏病中的作用与应用前景进行综述。     

Mesenchymal stem cells: future source for reparative medicine

Current treatments for ischemic cardiomyopathy are aimed toward minimizing the deleterious consequences of damaged myocardium. The possibility of treating heart failure by generating new myocardium and vascular structures has provided major impetus for recent stem cell research. Mesenchymal stem cells (MSCs), also referred to as marrow stromal cells, differentiate into a wide variety of lineages, including myocardial smooth muscle and possibly endothelial cells. The multilineage potential of MSCs, their ability to elude detection by the host's immune system, and their relative ease of expansion in culture make MSCs a very promising source of stem cells for transplantation. This paper reviews animal and human trials studying the role of MSCs in cardiomyogenesis and vasculogenesis in postinfarct myocardium, factors that stimulate MSC differentiation, routes of MSC delivery, and methods of detecting MSC engraftment.     

间充质干细胞的生物特性及其在冠心病治疗中的临床应用

间充质干细胞(m esenchym al stem cells,MSCs)是一些易于在体外扩增并且具有多种分化能力的原始细胞,它在适宜的环境中可以分化为骨、软骨、脂肪、纤维结缔组织、骨髓基质等不同细胞。已有大量试验研究MSCs的分离、纯化、培养,以及它的特性,并有临床前期的研究实验证实了MSCs对冠心病的治疗效果,现将上述国内外研究现况予以综述,并对尚未明确的相关问题进行探讨。