脐带间充质干细胞治疗17例类风湿性关节炎患者的临床疗效观察

目的:本文应用脐带间充质干细胞(Umbilical Cord Mesenchymal stem cell,UC-MSC)探讨治疗RA的疗效,为临床治疗RA寻找新途径。方法:采用脐带间充质干细胞静脉输注的方式,细胞数为1×107/人次,对17例RA患者进行疗效观察。2例类风湿合并强直性脊柱炎病人同时还采用局部注射。结果:全部患者在饮食、睡眠、体力、疲劳等临床症状方面均有明显改善;全部患者满足ACR20标准,15例患者28个关节的疾病活动度评分(DAS28)3.2;12例患者满足ACR70标准,DAS28评分2.6;1例JRA患者,脐带间充质干细胞治疗4天后发热、皮疹消退,多关节疼痛得到控制。治疗前后患者血常规、肝肾功、血清免疫球蛋白及补体C3、C4检测结果无显著变化。结论:脐带间充质干细胞具有免疫调节、阻止炎性介质释放、减轻组织损伤等重要作用,可减轻和缓解RA的临床症状,且脐带间充质干细胞治疗对人体各项指标无明显改变,安全性很好,为临床治疗RA,寻找到一条新途径。     

胎盘间充质干细胞的应用研究

背景：胎盘间充质干细胞因其具有来源广泛、免疫原性低、不涉及伦理问题等优点成为种子细胞的新来源。 目的：阐述胎盘间充质干细胞的来源、生物学特性及应用最新研究进展。 方法：检索 PubMed、ScienceDirect、OvidSP、CNKI 数据库相关文章,检索时限为2003至 2015年,英文检索词为“Placenta,Mesenchymal stem cells,The placenta mesenchymal stem cells, Cell transplantation , Application mechanism”,中文检索词为“胎盘,间充质干细胞,胎盘间充质干细胞,细胞移植,应用机制”,从中筛选出与主题相关且论据可靠的部分文献,最终纳入57篇文章进行归纳综述。 结果与结论：目前已成功分离培养出胎盘间充质干细胞,并对其生物学特性进行研究,证明其具有干细胞源性及多向分化潜能。目前有较多关于胎盘间充质干细胞应用于实验动物及临床的研究,在骨组织工程、血管再生及神经组织等修复过程中均显示出了巨大的潜力,但胎盘间充质干细胞的具体应用机制目前尚不清楚,尚处于探索阶段,在胎盘间充质干细胞广泛应用于临床之前,仍有许多问题有待进一步研究明确,以确保其安全性和有效性。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

间充质干细胞用于类风湿关节炎治疗的理论及应用前景

类风湿关节炎(rheumatoid arthritis, RA)是一类以慢性多关节滑膜炎、骨及软骨破坏为主要特征的全身性自身免疫性疾病.     

人骨髓间充质干细胞的生物学特性

目的 建立人胚骨髓间充质干细胞(MSCs)分离及培养的方法，探讨体外培养MSCs的生物学特性．方法 通过密度梯度离心、贴壁法分离培养人胚MSCs，在倒置显微镜下连续观察细胞的形态变化．应用流式细胞术测定细胞周期和CD44、CD34、CD45表达，并研究其增殖及生长特征．结果 原代及传代培养显示，14代以前的MSCs具有活跃的增殖能力，细胞周期分析显示有82％的MSCs处于Gp／Gl期．MSCs阳性表达CD44，阴性表达CD34、CD45．结论 体外培养14代以前的的MSCs生长稳定，增殖较快，可作为组织工程的种子细胞．     

骨髓间充质干细胞下调类风湿性关节炎小鼠脾脏单个核细胞TLR8及TLR9的表达

背景：间充质干细胞能够缓解类风湿性关节炎小鼠的症状,但是其机制还不清楚。 目的：观察骨髓间充质干细胞对类风湿性关节炎小鼠脾脏单个核细胞表达TLR8及TLR9等的影响。 方法：DBA/1J小鼠随机分3组,非造模组不造模,阳性对照组和实验组制备Ⅱ型胶原诱导的小鼠类风湿性关节炎模型。实验组尾静脉注射移植大鼠骨髓间充质干细胞。 结果与结论：与阳性对照组比较,实验组小鼠关节直径明显减小,关节炎症细胞浸润程度明显降低,但比非造模组略高;小鼠脾脏单个核细胞表达TLR8、TLR9和白细胞介素1β的水平较阳性对照组明显降低(P < 0.01或P < 0.05);阳性对照组与实验组中TLR8与TLR9的表达均无明显相关性(P > 0.05)。说明骨髓间充质干细胞下调了类风湿关节炎小鼠脾脏单个核细胞表达TLR8及TLR9的水平,但TLR8与TLR9的表达无相关性。     

脂肪与骨髓来源间充质干细胞生物学特性的比较

背景：近几年来脂肪来源的间充质干细胞因其取材容易也被广泛研究。 目的：比较脂肪来源和骨髓来源间充质干细胞的生物学特性。 方法：分离及体外培养人骨髓源间充质干细胞和脂肪源间充质干细胞,比较它们的表型、细胞倍增时间及分泌因子水平等。 结果与结论：脂肪来源和骨髓来源的间充质干细胞在细胞表型上类似,只有CD106的表达有差异。脂肪来源间充质干细胞增殖速率比骨髓来源的间充质干细胞快。在相同体积的脂肪组织中能够得到的干细胞前体细胞的数量是骨髓的10倍以上。提示脂肪来源和骨髓来源的间充质干细胞具有相同功能,但脂肪组织是一个更有应用前景的干细胞来源。     

间充质干细胞在自身免疫性疾病中的应用研究进展

自身免疫性疾病（AID）的发病机制主要在于机体自身耐受的破坏,机体产生自身抗体和（或）自身反应性淋巴细胞,导致疾病的发生。目前临床上对AID的治疗主要是采取非特异性免疫抑制。虽然一定程度上可减轻症状,但不能根治疾病,而重症AID缺乏理想的治疗方法,预后差。因此,寻找有效的治疗方法仍然是目前临床亟待解决的问题。间充质干细胞（MSC）是一种非造血多能成体干细胞,具有多向分化以及促进组织修复等潜能,其免疫调控作用的发现是近年来干细胞研究领域的一项重要突破。最近,MSC移植治疗自身免疫性疾病的应用研究不断涌现,显示了MSC的免疫调节特性及其治疗AID的潜在能力,为进一步研究奠定了基础。     

间充质干细胞的细胞表型及免疫学研究进展

间充质干细胞具有多分化潜能,参与构成骨髓的微环境,分泌大量细胞因子支持造血。最近的研究显示间充质干细胞免疫表型呈现动态的表达;同种异体细胞移植免疫排斥由于移植抗原差异而引起,但同种异体间充质干细胞却具有免疫抑制作用。综述了其可能的机制及作为组织工程种子细胞的间充质干细胞具有独特的生物学特性。     

骨髓间充质干细胞免疫学特性的研究进展

随着免疫学和移植学的发展,人类对自身免疫性疾病认识的不断提高和对器官移植的日益接受,免疫抑制剂在临床医学中的应用愈来愈广泛。它们能提高患者的生存质量,延长患者的寿命,但是其昂贵的费用、易引起感染和肿瘤等的副作用明显地限制了它的临床应用。为此,免疫学专家和移植学专家一直在探索理想的诱导特异性耐受的方法和途径,以便减少免疫抑制剂的应用剂量和副作用,乃至部分或甚至完全替代免疫抑制剂。近20多年来,成体干细胞的可塑性现象引起人们的极大兴趣。其中骨髓间充质干细胞(bone marrow mesenchymal stemcell,MMSC)的功能作用和…     

Autologous stem cell transplantation in the treatment of refractory rheumatoid arthritis

The concept of using high-dose immunosuppressive treatment (HDIT) with autologous stem cell transplantation (ASCT) to treat patients with refractory rheumatoid arthritis has been provided by animal studies and anecdotal case reports. Over the past five years, an increasing number of patients with refractory rheumatoid arthritis have received HDIT with ASCT as an adjunct to intense immunosuppression. Here, we present a case of refractory rheumatoid arthritis in a 54-yr-old woman using HDIT with ASCT. Peripheral blood stem cells were mobilized with cyclophosphamide (4 g/m(2)) followed by G-CSF (5 microg/kg/day). Leukapheresis continued daily until the number of harvested progenitor cells reached 2 x 10(6) CD34+ cells/kg after CliniMax CD34+ positive selection. For HDIT, high-dose cyclophosphamide (total dose 200 mg/kg) and antithymocyte globulin (total dose 90 mg/kg) were administered and CD34+ cells were infused 24 hr after HDIT. The patient tolerated the treatment well but experienced an episode of neutropenic fever. She achieved an early dramatic improvement of joint symptoms during therapy. Fifty percent of improvement of rheumatoid arthritis by the American College of Rheumatology (ACR 50) preliminary definition was fulfilled during the 6 months following ASCT. Although further long-term follow-up is required, the patient's activity of arthritis has been stable since receiving HDIT with ASCT.     

间充质干细胞治疗脊髓小脑性共济失调

背景：脊髓小脑性共济失调是临床上较常见的以进行性加重的四肢共济运动障碍为主要临床表现的中枢神经系统变性疾病,常规药物治疗效果欠佳。 目的：观察自体骨髓间充质干细胞以及异体脐带间充质干细胞输注治疗脊髓小脑性共济失调的临床效果。 方法：对接受间充质干细胞治疗的27例确诊脊髓小脑性共济失调患者进行综合统计分析,其中6例行自体骨髓间充质干细胞腰穿治疗,21例行异体脐带间充质干细胞腰穿结合静脉输注治疗,两组患者均采用世界神经病联合会国际合作共济失调量表(International Cooperative Ataxia Rating Scale,ICARS)对患者治疗前后神经功能进行评定。 结果与结论：所有27例脊髓小脑共济失调患者行间充质干细胞治疗过程中以及治疗前后均未及明显不良反应。其中6例患者采用自体骨髓间充质干细胞治疗后效果均不明显,另外21例患者行异体脐带间充质干细胞输注治疗,治疗后3个月与治疗前比较,患者自觉症状均有一定程度改善,ICARS评分明显降低(P < 0.05)。说明脐带间充质干细胞治疗是安全的,可以一定程度地改善脊髓小脑性共济失调患者的临床症状,提高患者生活质量。     

Mesenchymal stem cells for the treatment of neurodegenerative disease

Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed.     

Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice

Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.     

Mesenchymal stem cells

The tremendous capacity of bone to regenerate is indicative of the presence of stem cells with the capability, by definition, to self-renew as well as to give rise to daughter cells. These primitive progenitors, termed mesenchymal stem cells or bone marrow stromal stem cells, exist postnatally, and are multipotent with the ability to generate cartilage, bone, muscle, tendon, ligament, and fat. Given the demographic challenge of an ageing population, the development of strategies to exploit the potential of stem cells to augment bone formation to replace or restore the function of traumatized, diseased, or degenerated bone is a major clinical and socioeconomic need. Owing to the developmental plasticity of mesenchymal stem cells, there is great interest in their application to replace damaged tissues. Combined with modern advances in gene therapy and tissue engineering, they have the potential to improve the quality of life for many. Critical in the development of this field will be an understanding of the phenotype, plasticity, and potentiality of these cells and the tempering of patients' expectations driven by commercial and media hype to match current laboratory and clinical observations.     

Mesenchymal stem cells transplantation in the treatment of radiation skin lesions

Transplantation of mesenchymal stem cells, both at early and later stage after local exposure of rats source beta radiation dose, 90Sr/90Y 140 GR, stimulates recovery of damaged skin. Diminution area local radiation injuries and accelerate healing radiation ulcers. Clinically shows the high efficiency of the transplantations autologous mesenchymal stem cells in treatment of deep beam ulcers, intractable standard conservative treatment. Found promising application of mesenchymal stem cells for treatment of severe local radiation injuries and the need to develop the best possible conditions for their use.     

间充质干细胞在炎症免疫调节中的作用及应用进展

背景：研究表明,间充质干细胞的主要功能有直接参与损伤修复,分泌生长因子,调节免疫和炎症,抗氧化应激等,可用于治疗多种急、慢性疾病。 目的：综述间充质干细胞在炎症免疫调节中的研究进展。 方法：以“干细胞,间充质干细胞,免疫调节,炎症,免疫细胞,炎症因子,治疗”为中文检索词,以“stem cells,mesenchymal stem cells,immune regulation,inflammation,immune cells,inflammatory factors,treatment”为英文检索词,在万方、中国知网期刊全文数据库和PubMed数据库检索2005年1月至2015年8月有关干细胞参与炎症免疫调节的文献。排除陈旧性和重复性研究,最终纳入40篇文献进行综述。 结果与结论：间充质干细胞因其具有免疫调节及多向分化的特性,越来越受到临床的重视,同时间充质干细胞易于从不同组织中获取并且具有良好的体外扩增能力,使得其在组织损伤炎症与修复的临床运用中具有广阔的前景。作为最有希望进入临床应用阶段的种子细胞,间充质干细胞在许多疾病的治疗中表现出了它的优越性,特别是对于免疫调节失衡导致的炎症性相关疾病的治疗中表现出良好的效果。相信在未来的细胞生物治疗领域,间充质干细胞将占有重要的地位。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Mesenchymal stem cells in tissue engineering

The repair of diseased or damaged cartilage remains one of the most challenging problems of musculoskeletal medicine. Tissue engineering advances in cartilage repair have utilized autologous and allogenic chondrocyte and cartilage grafts, biomaterial scaffolds, growth factors, stem cells, and genetic engineering. The mesenchymal stem cell has specifically attracted much attention because of its accessibility, potential for differentiation, and manipulability to modern molecular, tissue and genetic engineering techniques. Mesenchymal stem cells provide invaluable tools for the study of tissue repair when combined with a carrier vehicle/matrix scaffold, and/or bioactive growth factors. However, an underappreciated source of knowledge lies in the relationship between fetal development and adult tissue repair. The multitude of events that take place during fetal development which lead from stem cell to functional tissue are poorly understood. A more thorough understanding of the events of development as they pertain to cartilage organogenesis may help elucidate some of the unknowns of adult tissue repair.