间充质干细胞在神经系统疾病中的应用

间充质干细胞（Mesenchymal stem cells,MSCs）是一种中胚层发育的早期细胞,为重要的多潜能干细胞,主要存在于全身结缔组织器官中,具有多向分化的潜能。可分化为中胚层起源的多种组织细胞,如成骨细胞、软骨细胞、脂肪细胞等;在适宜条件下也可跨组织分化为神经细胞等,并具有相应功能。本文主要对近年来MSCs在神经系统疾病治疗中的潜在作用作一综述。     

大鼠骨髓间充质干细胞在急性肝损伤环境中的分化

骨髓中除造血干细胞（HSCs）外，还存在着另外一类干细胞，即间充质干细胞（MSCs）。目前研究表明，MSCs具有横向分化能力，尤其能诱导分化为肝细胞，成了肝干细胞研究的热点，也为临床治疗终末期肝病提供了新思路。目前报道肝脏疾病影响17．5％的人群，终末期肝病的治疗在临床尚没有可行的办法。因此，迫切需要建立一种更有效的治疗方法。本研究探讨了骨髓MSCs在急性肝损伤环境中的分化。     

间充质干细胞在系统性硬化的应用前景

间充质干细胞(mesenchymal stem cells,MSCs)多存在于骨髓中,是一类具有多向分化能力及免疫调节作用的细胞.近年来,MSCs在自身免疫性疾病中的应用受到很大关注.研究表明,MSCs分化为血管内皮细胞的能力受损在系统性硬化(systemic sclerosis,SSc)的病理改变中起重要作用.同时,...     

间充质干细胞在糖尿病细胞疗法中的研究现状

间充质干细胞(mesenchymal stem cells,MSCs)是一类具有自我更新和多向分化潜能的细胞,在细胞替代治疗中有极其重要的作用.MSCs来源广泛,几乎所有的成体和胚胎组织中都有MSCs [1].目前研究较多的是骨髓、脂肪、滑膜、脐带血、胎肝、羊膜等来源的MSCs.MSCs最重要的特性是多能性,能分化成多种不同的细胞谱系,如骨、脂肪、软骨等间质细胞谱系,以及神经元、肝细胞和内皮细胞等内胚层和神经外胚层细胞[2-3].MSCs同样具有分化为胰岛内分泌细胞的可塑性,已经证实来源于各组织中的MSCs可以分化为有功能的胰岛素分泌细胞.本文就MSCs分化为胰岛样细胞的方法 和分化机制做一综述.     

间充质干细胞与糖尿病慢性并发症

间充质干细胞（MSCs）具有多向分化能力，由于MSCs的分化细胞类型与糖尿病慢性并发症损伤的细胞类型吻合，近年来越来越多的研究针对MSCs在糖尿病慢眭并发症发病机制中的作用。糖尿病时高血糖可能通过影响MSCs的细胞分化类型而导致糖尿病多种并发症的发生。从MSCs多向分化潜能的角度解释糖尿病慢性并发症的发病机制为其治疗提供了新的思路，具有重要的临床意义。     

间充质干细胞外泌体作用及机制的研究进展

［摘要］　间充质干细胞（MSCs）具有多向分化和旁分泌生物活性因子的功能,从而在免疫调节、抗炎、血管生成和抗凋亡等方面发挥作用,广泛应用于临床的细胞治疗中。MSCs来源的外泌体既可携带MSCs的遗传信息,又比MSCs更易于储存和维持MSCs的功能,有利于多种组织损伤后的修复与再生。该文就MSCs及其外泌体生物学特性及功能、MSCs外泌体在不同疾病中的作用及机制作一综述。     

间充质干细胞对心肌损伤修复的研究进展

在过去的10年中,干细胞已成功地应用于治疗各种疾病:胰岛移植治疗糖尿病;利用胚胎神经前体细胞和神经干细胞治疗神经系统疾病(帕金森综合征、癫痫、休克、脊髓损伤);肝细胞和肝的干细胞治疗肝脏疾病.近几年,干细胞移植治疗缺血性心脏病已成为一个热点话题.大量的动物实验和前期临床试验表明这种治疗对心肌细胞再生和心脏血流动力学改变有着明显的疗效.在各种干细胞中,由于骨髓间充质干细胞(mesenchymal stem cells, MSCs)具有取材方便、体外易培养和可诱导分化的特点,对其研究更加广泛和深入.现对MSCs在治疗心肌病中的应用作一综述.     

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.     

骨髓间充质干细胞诱导分化成骨骼肌细胞研究现状

骨髓间充质干细胞（MSCs）是具有多向分化能力的干细胞，主要分布于结缔组织和组织器官，以骨髓中含量最丰富。在不同的诱导条件下，其有向成骨细胞、成肌细胞、成软骨细胞、肌腱细胞、脂肪细胞和基质细胞等中胚层细胞分化的能力。因此，这为治疗心血管疾病、神经系统疾病、肌组织和骨关节疾患提供了一条全新的探索之路。现将MSCs诱导分化成骨骼肌细胞的研究进展作一综述。     

三七皂甙诱导骨髓基质细胞分化为心肌样细胞的实验研究

目的探讨三七皂甙对体外定向诱导猪骨髓基质细胞(MSCs)分化为心肌样细胞的影响。方法用穿刺方法抽取猪骨髓,分离并培养骨髓基质细胞,中药三七皂甙定向诱导分化为心肌样细胞。倒置显微镜下观察细胞形态,免疫细胞化学法鉴定心肌细胞特异性抗原标志物肌钙蛋白T,用RT-PCR对心肌肌球蛋白重链(β-MHC)进行鉴定。取培养的猪心肌细胞作为阳性对照,未经三七皂甙诱导正常培养的骨髓基质细胞作为阴性对照。结果猪MSCs经三七皂甙诱导2h后,大部分MSCs可分化为心肌样细胞,免疫细胞化学检测细胞中的肌钙蛋白T呈阳性,RT-PCR显示能表达β-MHC。结论MSCs是骨髓来源的具有多向分化潜能的干细胞,在三七皂甙的定向诱导下,可以向心肌样细胞分化,有望成为心衰及心肌梗死等心肌损伤时干细胞移植治疗的理想细胞材料。     

Mesenchymal stem cells and their potential as cardiac therapeutics

Mesenchymal stem cells (MSCs) represent a stem cell population present in adult tissues that can be isolated, expanded in culture, and characterized in vitro and in vivo. MSCs differentiate readily into chondrocytes, adipocytes, osteocytes, and they can support hematopoietic stem cells or embryonic stem cells in culture. Evidence suggests MSCs can also express phenotypic characteristics of endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte cells. When introduced into the infarcted heart, MSCs prevent deleterious remodeling and improve recovery, although further understanding of MSC differentiation in the cardiac scar tissue is still needed. MSCs have been injected directly into the infarct, or they have been administered intravenously and seen to home to the site of injury. Examination of the interaction of allogeneic MSCs with cells of the immune system indicates little rejection by T cells. Persistence of allogeneic MSCs in vivo suggests their potential "off the shelf" therapeutic use for multiple recipients. Clinical use of cultured human MSCs (hMSCs) has begun for cancer patients, and recipients have received autologous or allogeneic MSCs. Research continues to support the desirable traits of MSCs for development of cellular therapeutics for many tissues, including the cardiovascular system. In summary, hMSCs isolated from adult bone marrow provide an excellent model for development of stem cell therapeutics, and their potential use in the cardiovascular system is currently under investigation in the laboratory and clinical settings.     

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。     

Mesenchymal stem cells: heading into the clinic

In recent years, there has been an increasing interest in non-hematopoietic pluripotent progenitor cells that are found in the bone marrow. Mesenchymal stem cells (MSCs) are the first non-hematopoietic progenitors to be isolated from the bone marrow and extensively characterized. In addition to their ability to support hematopoiesis, MSCs can differentiate into osteocytes, chondrocytes, tenocytes, adipocytes and smooth muscle cells. This article will review our current understanding of bone marrow stroma and MSCs and their potential therapeutic role in the setting of hematopoietic stem cell transplantation.     

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.     

Cell-to-cell contact induces mesenchymal stem cell to differentiate into cardiomyocyte and smooth muscle cell

BACKGROUND: Recent evidences have suggested that stem cell can differentiate into cardiomyocyte and smooth muscle cell (SMC) in vivo or in vitro. But the mechanism on how stem cell differentiates is still unknown. We investigated whether intercellular interaction or soluble chemical factors would induce mesenchymal stem cells (MSCs) to acquire the phenotypical characteristics of cardiomyocytes or SMC. METHODS: MSCs were isolated from rat bone marrow with density gradient centrifugation and amplified in vitro. Flow cytometry was used to monitor the expression of surface antigen profile. After labeled by GFP (green fluorescent protein) transfection, rat MSCs were used to culture with adult rat cardiomyocytes and rat aortic SMCs in direct co-culture, indirect co-culture and conditioned culture, respectively. One week later, immunofluorescence staining against alpha-actin, desmin, and cardiac troponin T (cTnT) for cardiomyocyte, smooth muscle calponin and SM-alpha-actin for SMC were performed. RESULTS: Immunofluorescence staining was positive against alpha-actin, desmin, and cTnT on MSCs in co-culture group with adult cardiomyocytes, positive against smooth muscle calponin and SM-alpha-actin on MSCs in co-culture group with SMCs. In contrast, no alpha-actin, desmin, and cTnT expression was observed in the indirect co-culture group and conditioned culture group; no smooth muscle calponin and SM-alpha-actin in the indirect co-culture group and conditioned culture group. CONCLUSIONS: Direct cell-to-cell contact between MSC and adult cardiomyocyte or SMC, but not the soluble signaling molecules is obligatory in the differentiation of MSC into cardiomyocytes or SMC.     

Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34⁺ hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34⁺ grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.     

Mesenchymal stem cells and haematopoietic stem cell transplantation

The bone marrow serves as a reservoir for different classes of stem cells. In addition to haemopoietic stem cells, the bone marrow comprises a population of marrow stromal cells or mesenchymal stem cells (MSCs). These cells exhibit multilineage differentiation capacity, and are able to generate progenitors with restricted developmental potential, including fibroblasts, osteoblasts, adipocytes and chondrocyte progenitors. In addition, MSCs have been shown to possess immunosuppressive activity in vitro and in vivo. Clinical trials are underway to test whether MSCs are beneficial in patients undergoing allogeneic bone marrow transplantation. With the expanding role of stem cell transplants in different areas of medicine, including cardiology and orthopaedics, MSCs may become very important in the next few years.     

Mechanisms of Immunomodulation by Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) have been identified in animals, especially in bone marrow. As stem cells, they have the ability to differentiate into multiple cell types. This potential raises exciting therapeutic possibilities. A recent report described the successful use of MSCs for the treatment of graft-versus-host disease; however, the scientific community has yet to define the molecular mechanisms of immunomodulation by MSCs. This review summarizes what is known and discusses the conflicting data with regard to the mechanisms of immunomodulation by MSCs.     

Hematopoietic stem cell origin of mesenchymal cells: opportunity for novel therapeutic approaches

There has been a general belief that there are two types of adult stem cells, i.e., hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), each with distinctly different functions. According to this dogma, HSCs produce blood cells, while MSCs are thought to generate a number of non-hematopoietic cells including fibroblasts, adipocytes, chondrocytes and bone cells. Recently, a number of studies, including those in our laboratory based on single HSC transplantation, blurred the clear distinction between HSCs and MSCs and strongly suggested an HSC origin of the adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and the literature pointing out the vagary in the stem cell nature of MSCs. The concept of the HSC origin of mesenchymal cells will have many immediate and long-term impacts on the therapies of diseases and injuries of the connective tissues.     

Mesenchymal stem cells in the treatment of chronic lung disease

Mesenchymal stem cells (MSCs) are a populace of non‐haematopoietic multipotent stromal cells, which have the ability to differentiate into tissue derived from a single germ layer. MSCs have been isolated from various sites, including adipose tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but are most often isolated from bone marrow. MSCs have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine, including the secretion of anti‐inflammatory cytokines and growth factors, the migration of cells to the site of injury when administered and the ability to ‘rescue’ cells through the transfer of functional mitochondria. They also offer the possibility of autologous cell transplantation, circumventing immune rejection. These properties, among others, make MSCs a promising potential therapeutic agent in the treatment of chronic lung diseases with high rates of morbidity and mortality, such as idiopathic pulmonary fibrosis (IPF), COPD and obstructive bronchiolitis (OB). Numerous animal models have shown the protective and reparative effects of MSCs in models of experimental lung injury. There are currently several clinical trials underway to evaluate the safety and efficacy of MSCs in the treatment of IPF, COPD and OB. While early results are encouraging, a considerable amount of research must be done concerning the safety MSCs, as well as their optimal dosage, time and route of administration. In addition, much is still unknown about the pathogenesis of these chronic lung diseases, as well as the mechanisms MSCs utilize to assist in their repair.