间充质干细胞治疗糖尿病的研究进展

糖尿病是目前困扰人类健康的第三大杀手。胰岛移植作为糖尿病的一种有效方法早已得到公认,但是胰岛供体的缺乏和移植排斥反应的存在限制了胰岛移植的临床应用[1]。胰岛素替代疗法是目前治疗糖尿病最有效的方法。然而这种方法也有许多缺陷。间充质干细胞(mesenchymal stem cell,MSC)具有多向分化潜能的均质性细胞,具有供源丰富、易于获得、有自由供体、避免免疫排斥等优点,因而是较为理想的胰岛B细胞来源[2]。近年来,众多实验研究表明了通过诱导MSC分化为胰岛B细胞治疗糖尿病的可能性。     

脂肪来源间充质干细胞体外定向诱导分化血管细胞的研究进展

脂肪来源的间充质干细胞具有较强的体外增殖能力,因具有生物学特性稳定、来源充足、体外培养条件低等优势已引起各国学者的关注。脂肪间充质干细胞凭借其多向分化潜能,是人体干细胞库潜在的重要来源之一。目前,研究人员已成功地在体外将其诱导为内皮细胞,成骨细胞、成软骨细胞、脂肪前体细胞、平滑肌细胞,心肌细胞、神经样细胞等。就脂肪来源的间充质干细胞体外定向诱导分化血管细胞的研究进展作一综述。     

间充质干细胞在造血干细胞移植中的应用

间充质干细胞(MSCs)是一种具有自我更新和多向分化潜能的成体干细胞,存在于骨髓、脂肪组织、脐血及多种胎儿组织.它可分泌多种细胞因子及生长因子,促进造血干细胞(HSC)的增殖与分化.MSCs还具有免疫调节、抗炎和组织修复作用,可减轻移植物抗宿主病(GVHD)及其他移植相关并发症.     

间充质干细胞在治疗癫痫所致炎症反应中的作用研究进展

间充质干细胞(MSCs)的免疫调节功能成为近年来的研究热点之一。癫痫是一种以反复发作为特征的复杂性神经系统疾病,而炎症反应是癫痫发生和反复发作的一个重要因素。研究表明,MSCs能够有效治疗多种退行性疾病造成的炎性反应,且发现MSCs可以通过炎症微环境发挥免疫调节功能。简要综述了MSCs在治疗癫痫所致炎症中的作用,旨在为临床应用MSCs防治癫痫提供理论依据。     

间充质干细胞治疗糖尿病下肢缺血研究进展

糖尿病下肢缺血是一种严重的糖尿病并发症,可导致下肢感染、溃疡和坏死,严重时甚至需要截肢.传统治疗和外科治疗在临床上亦有诸多局限性,随着以干细胞治疗为主的再生医学兴起,为糖尿病下肢缺血的治疗带来新的可能性.糖尿病下肢缺血的干细胞治疗中最引人瞩目的是间充质干细胞(MSC).MSC是一类具有多向分化潜能且低免疫原性的细胞,通...     

真皮间充质干细胞的研究进展

间充质干细胞(mesenchymal stem cells,MSC)是一类具有多向分化潜能和高度自我复制能力的组织干细胞,来源于发育早期的中胚层和外胚层。MSCs最初在骨髓中发现,随后发现在个体发育的其他组织中也存在该细胞。本世纪初有研究者从幼年和成年的啮齿动物皮肤真皮组织中分离得到了干细胞,并称之为皮肤前体细胞。随后,从胎儿、成人、老年供体的真皮结缔组织中得到了有跨胚层分化潜能的MSCs,第一次真正意义上证实了真皮组织中确实存在MSCs,并命名为真皮间充质干细胞(dermis mesenehymal stem cells,DMSCs)。本文就DMSCs的分离、培养、生物学特性及其临床应用前景做一综述。     

内源性骨髓间充质干细胞在肺纤维化中的研究进展

肺纤维化是多种病因引起的累及肺间质、肺泡、细支气管的肺部慢性、弥漫性、间质性肺疾病,尚无有效的治疗药物.目前,外源性骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells,BM-MSCs)移植作为一种新的干细胞疗法在治疗肺纤维化中的作用备受关注.目前对肺纤维化过程中内源性...     

间充质干细胞分化为内皮细胞的意义和细胞学基础

间充质干细胞(mesenchymalstemcells,MSCs)主要存在于骨髓中,是多潜能干细胞,在脐血、外周血、脂肪、皮肤等多种组织中也相继分离出MSCs。MSCs具有独特的免疫特性,在异种异体环境内长期存在,使其临床应用前景更为广泛。目前,MSCs的分离培养、诱导分化及鉴定体系已趋成熟,理论上可分化为所有中胚层来源的细胞,内皮细胞来源于中胚层,因此MSCs具有分化为内皮细胞的可能性。本文对MSCs内皮分化意义和细胞学基础及其新近的研究进展作一综述。     

Isolation,growth requirements,cloning, prostacyclin production and life-span of human adult endothelial cells in low serum culture medium

Summary Endothelial cells from autopsy and biopsy specimens from a variety of adult human vascular tissue were harvested by collagenase treatment and gentle swabbing of the lumenal surface. Nutrient medium MCDB 107 containing a partially purified brain-derived growth factor (5 μg/ml), epidermal growth factor (10 ng/ml) and only 2% (v/v) fetal bovine serum supported clonal and long-term serial culture (17.6 to 26.1 cumulative population doublings) of endothelial cells from vena cava, thoracic aorta and tibial arteries at a 70% rate of success. Cumulative doublings of the cell population from eight cultures were inversely proportional to age of donor of the vascular tissue from which cells were isolated. Heparin had an enhancing effect on cell growth that varied with cell strain. Prostacyclin production of human adult endothelial cell cultures was stimulated by aracidonate and thrombin by 17 to 20 and 2 to 3-fold respectively. Endogenous and stimulated rates of prostacyclin production by human adult endothelial cells were 2 to 3 times that of human adult smooth muscle cells and 20 to 30 times that of human fibroblasts. The work was supported by Public Health Service Grant AGO3275 and Grant No. 1718 from the Council for Tobacco Research. Editor's statement This paper provides an opportunity for relatively rapid, easy growth and cloning of endothelial cells from various human specimens which are more difficult to deal with than those obtained from an intact artery or intact umbilical vein. Russel Ross     

Biological characteristics of foam cell formation in smooth muscle cells derived from bone marrow stem cells

Bone marrow mesenchymal stem cells (BMSC) can differentiate into diverse cell types, including adipogenic, osteogenic, chondrogenic and myogenic lineages. There are lots of BMSC accumulated in atherosclerosis vessels and differentiate into VSMC. However, it is unclear whether VSMC originated from BMSC (BMSC-SMC) could remodel the vessel in new tunica intima or promote the pathogenesis of atherosclerosis. In this study, BMSC were differentiated into VSMC in response to the transforming growth factor β (TGF-β) and shown to express a number of VSMC markers, such as α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain1 (SM-MHC1). BMSC-SMC became foam cells after treatment with 80 mg/L ox-LDL for 72 hours. Ox-LDL could upregulate scavenger receptor class A (SR-A) but downregulate the ATP-binding cassette transporter A1 (ABCA1) and caveolin-1 protein expression, suggesting that modulating relative protein activity contributes to smooth muscle foam cell formation in BMSC-SMC. Furthermore, we found that BMSC-SMC have some biological characteristics that are similar to VSMC, such as the ability of proliferation and secretion of extracellular matrix, but, at the same time, retain some biological characteristics of BMSC, such as a high level of migration. These results suggest that BMSC-SMC could be induced to foam cells and be involved in the development of atherosclerosis.     

Comparative endocrinology-paracrinology-autocrinology of human adult large vessel endothelial and smooth muscle cells

Summary Endothelial and smooth muscle cells were isolated from human adult large blood vessels to compare their proliferative response to hormones and growth factors. Neural extracts and the medium from differentiated hepatoma cells were used as concentrated sources of required hormones and growth factors that supported both cell types. Active hormones and growth factors were identified from the neural extracts and hepatoma medium by substitution or direct isolation and biochemical characterization. Epidermal growth factor, lipoproteins, and heparin-binding growth factors elicited growth-stimulatory effects on both endothelial and smooth muscle cells. Both types of human vascular cells displayed 7600 to 8600 specific heparin-binding growth factor receptors per cell with a similar apparent dissociation constant (Kd) of 200 to 250 pM. Heparin modified the response of both endothelial and smooth muscle cells to heparin-binding growth factors dependent on the type of heparin-binding growth factor and amount of heparinlike material present. In addition, heparin exerted a growth factor-independent inhibition of smooth muscle cell proliferation. Platelet-derived growth factor, insulinlike growth factors, and glucocorticoid specifically supported proliferation of smooth muscle cells with no apparent effect on endothelial cell proliferation. Growth-factorlike proteinase inhibitors had an impact specifically on endothelial cell proliferation. Transforming growth factor beta was a specific inhibitor of endothelial cells, but had a positive effect on smooth muscle cell proliferation. The results provide a framework for differential control of the two vascular cell types at normal and atherosclerotic blood vessel sites by the balance among positive and negative effectors of endocrine, paracrine and autocrine origin. This research was supported by NIH grants CA37589, HL33847, and AM35310 from the National Institutes of Health, Bethesda, MD; grant 1718 from the Council for Tobacco Research; and a grant from RJR/Nabisco, Inc.     

MicroRNA对动脉粥样硬化发生的调控作用及其临床应用

MicroRNA（miRNA）是新发现的基因表达调控因子,由长约21～25个核苷酸的单 链RNA分子构成,是非编码小RNA. 它可以通过与特定mRNA的3′非翻译区（3′- untranslated region,3′UTR）相结合,抑制mRNA编码蛋白质的翻译过程来调控基因表达. 动脉粥样硬化(atherosclerosis, AS)是一种慢性炎症性疾病,是多种心血 管疾病的病理基础.最近,研究发现多个miRNA与动脉粥样硬化的发生发展有关, 且其在血液和体液中稳定存在并高度保守. 本文主要综述了miRNA对动脉粥样硬化进程的调节作用及以其为靶点的相关临床研究,旨在阐明miRNA成为动脉粥样硬化诊断与治疗新靶点的重要意义.     

27nt-miRNA对间充质干细胞向血管平滑肌细胞分化的影响

为探讨27nt-miRNA对间充质干细胞向血管平滑肌细胞分化影响,构建27nt-miRNA过表达、反义序列Anti-27nt-miRNA以及阴性对照的表达质粒,慢病毒包装后分别转染人脐带间充质干细胞(hUCMSC),加入Ⅳ型胶原诱导hUCMSC定向分化为血管平滑肌细胞。四唑盐(MTT)比色法检测分化后细胞活力,免疫细胞化学染色法检测分化后细胞SM22α(兔抗平滑肌22α,smooth muscle 22α)的表达,Western印迹法和RT-PCR检测分化后细胞内的SMA (兔抗平滑肌肌动蛋白,smooth muscle actin) mRNA、SM 22α mRNA及其蛋白质表达情况。经检测,27nt-miRNA过表达分化组与阴性对照组相比,细胞活力下降20.48%(P0.05),SMA mRNA、SM22α mRNA及其蛋白质表达量明显升高(P0.05);而Anti-27nt-miRNA分化组细胞活力上升了18.07%(P0.05),SMA mRNA、SM22α mRNA及其蛋白质表达量下降(P0.05)。综上所述,27nt-miRNA能够促进间充质干细胞向血管平滑肌细胞分化,并且抑制分化后的细胞活力。