脂肪干细胞外泌体对人牙髓干细胞增殖与成骨分化的影响北大核心CSCD

目的观察人脂肪间充质干细胞来源外泌体对人牙髓干细胞增殖与成骨分化的影响。方法制备人脂肪来源的间充质干细胞和外泌体。将人牙髓干细胞随机分为3组,正常组进行常规培养,对照组进行成骨诱导分化,实验组在成骨诱导分化时添加5μg·mL^(-1)外泌体。用CCK-8法检测细胞增殖活性,用酶联免疫吸附实验法检测碱性磷酸酶活性,用Western blot法检测骨钙素和骨桥蛋白的表达情况。结果实验组、对照组和正常组的细胞相对增殖活性(光密度值)分别为0.54±0.02,0.34±0.01和0.32±0.01,碱性磷酸酶相对活性(光密度值)分别为10.37±1.26,4.89±0.94和0.71±0.03,骨钙素蛋白相对表达量分别为0.59±0.10,0.23±0.05和0,骨桥蛋白相对表达量分别为0.63±0.12,0.61±0.04和0,实验组的上述指标与对照组和正常组比较,差异均有统计学意义(均P<0.05)。结论人脂肪间充质干细胞来源的外泌体可促进人牙髓干细胞的增殖和成骨分化。     

人多能干细胞在药物发育毒性评价中的研究进展

发育毒性是毒理学研究中最具挑战性的领域之一,传统的发育毒性评价方法均存在实验成本高、周期长、技术复杂等弊端.人多能干细胞(hPSC)包括人胚胎干细胞(hESC)和诱导多能干细胞(iPSC),具有分化多能性和无限增殖的潜力.近年来hPSC在发育毒性评价方面的研究逐渐增多,主要从hPSCs培养中代谢小分子的变化、hPSCs...     

人乳牙牙髓基质干细胞的研究进展

人乳牙牙髓基质干细胞（SHED）的研究刚刚处于起步阶段，但其本身具有的多向分化潜能有着非常重要的研究价值。本文通过参考相关文献。结合诸多学者的研究成果，从人乳牙牙髓基质干细胞的研究基础、体外实验方法及牙髓基质干细胞生物学特性等方面对人乳牙牙髓基质干细胞的研究进展进行综述。     

胚胎干细胞与羊水干细胞

目前干细胞的再生潜能得到生物医学领域诸多学者的关注,胚胎干细胞再生潜能高但获取有悖于伦理,科学家转而研究其他成体干细胞,以利用其再生特性进行器官修复等。该文就羊水干细胞与胚胎干细胞的特性、比较及应用予以介绍。     

人源干细胞产品的药学评价考虑

干细胞具有自我更新(self-renewing)和多向分化(multilineage differentiation)潜能，且不同类型的干细胞具有各自不同的优势和局限性，在基础研究和临床应用中成为热点领域。按药品进行研发的人源干细胞产品目前主要来源于成体干细胞、人胚干细胞和诱导多能干细胞三大类。人源干细胞产品复杂多样，在多种疾病治疗中展现出独特的治疗优势。本文总结了人源干细胞产品的特点和最新的研究进展，并根据药品开发和技术评价的规律，围绕生产用原材料、生产工艺、质量研究与控制、稳定性和包装容器密封系统等方面提出现阶段的药学审评考虑和讨论，供业界和监管机构探讨交流，以期能促进此类产品的临床转化和应用。     

英科学家利用干细胞研制人造血

利用干细胞制成的血液将会改变输血现状，避免医学的供血短缺。而且能够拯救在战场和车祸中受伤者的生命。     

胚胎干细胞/诱导多能干细胞向间充质干细胞转化的研究进展

胚胎干细胞(ESCs)/诱导多能干细胞(iPSCs)因其有潜在成瘤性,制约了它的临床应用.间充质干细胞(MSCs)具有多向分化能力、免疫调节功能以及低免疫原性,且仍未发现它有成瘤性,因而成为干细胞治疗颇具临床应用价值的种子细胞.近年来研究发现应用合适的诱导方案可以从ESCs/iPSCs获取MSCs,结合ESCs/iPSCs的无限自我更新能力,ESCs/iPSCs向MSCs转化将可能是获取MSCs的一种数量充足且稳定的新来源.本文将对目前ESCs/iPSCs向MSCs转化的方法 、机制以及新衍生的MSCs的免疫调节功能、干性特征做一综述.     

外源性雌激素对人牙周膜干细胞骨分化能力影响的实验研究

目的：检测外源性雌激素对人牙周膜干细胞( PDLSCs )骨分化能力的影响。方法将体外培养的PDLSCs加入无酚红成骨诱导培养液和不同浓度的17β-E2[分为E10-7、E10-8、E10-9组和对照组(成骨诱导培养液+无水乙醇(0.01%)]-雌二醇[分为E10-7、E10-8、E10-9组、ICI组(成骨诱导培养液+ICI182780)、E10-7+ICI组(成骨诱导培养液+1×10-717β-E2+1×10-7ICI182780)],观察各组细胞形态、测定其增值水平、碱性磷酸酶(ALP)活性、Ⅰ型胶原合成能力。结果添加外源性雌激素后,细胞增殖加快,生长密集,呈螺旋状排列。 PDLSCs的增殖发生变化,与对照组相比,第3、5天雌激素干扰组细胞增殖受到抑制( P <0.05),此后雌激素干扰组细胞增殖高于对照组( P <0.05),在不同药物浓度组间,E10-7组对细胞增殖影响最为明显,其细胞增殖水平高于E10-8、E10-9组( P <0.05)。 ALP表达显示动态变化,自第3天开始,各组ALP表达均升高,而雌激素干扰组ALP表达量高于对照组( P <0.05),在不同药物浓度组间E10-7组ALP表达增加高于E10-8、E10-9组( P <0.05),与ICI组、E10-7+ICI组比较,差异无统计学意义( P >0.05);PDLSCsⅠ型胶原合成表达与对照组相比有增加趋势,且与药物浓度有剂量依赖关系。结论雌激素对PDLSCs成骨分化过程有促进作用,该作用与雌激素浓度密切相关。     

干细胞研究进展

干细胞不仅存在于胚胎发育时期 ,而且在成体内也广泛分布于各种不同组织器官的特定部位。在胚胎时期干细胞的功能主要是参与机体的发育 ,成年后则对维持组织器官的新陈代谢有重要作用。随着胚胎干细胞 ,神经干细胞等方面研究的不断深入 ,有关干细胞的研究已日益成为一个全球性的热点。本文仅就其进展做一简要综述。     

人胚胎生殖干细胞移植及心肌再生

目的 探讨直接注射移植人胚胎生殖(EG)细胞对大鼠心肌梗死的影响.方法 40只SO大鼠经缝扎左冠状动脉前降支,建立急性心肌梗死(AMI)模型,分干细胞移植组和对照组.取5～10周人胚胎牛殖腺嵴,组织块体外培养,生物学鉴定证实为人EG细胞,将其直接注入大鼠急性心肌梗死区边缘.移植后1 d,1、2、4周处死大鼠,采用免疫组化法观察心肌形成转录因子Nkx 2.5在移植细胞的表达.结果 移植组鼠抗人细胞核抗体MAB1281检测刚性,心肌形成转录因子Nkx2.5在移植细胞阳性表达.结论 人EG细胞胞接注入移植大鼠心肌梗死处,细胞能存活并呈现向心肌细胞分化的表型.     

间质干细胞与肿瘤的关系研究进展

间质干细胞(mesenchymal stem cells,MSCs)是来源于中胚层的一类具有高度自我更新能力和多向分化潜能的非造血干细胞,具有很好的组织迁移能力和肿瘤靶向性。MSCs用于抗肿瘤治疗已经开展了广泛的研究,MSCs可以作为细胞载体发挥抗肿瘤作用,同时通过促肿瘤血管生成、免疫抑制、分化为肿瘤相关成纤维细胞等方式促进肿瘤的恶性行为。该文对近年来该领域的研究进展进行简要综述。     

Neural stem cells and neurodegeneration

Neurodegenerative diseases, such as Parkinson's disease, are characterized by a continuous loss of specific populations of neurons. Possible regenerative interventions include transplanting developing neural tissue or neural stem cells into the host brain, and inducing proliferation of endogenous stem cells by pharmacological manipulations. Neural stem cells (NSC), with the capacity to self-renew and produce the major cell types of the brain, exist in the developing and adult central nervous system (CNS). These cells can be grown in vitro while retaining the potential to differentiate into nervous tissue. This review focuses on regenerative therapy in neurodegenerative diseases using NSC.     

Cardiac-derived stem cells

Current scientific dogma holds that cardiomyocyte stem cells do not exist in the adult mammalian heart, and furthermore, that there is little, if any, potential for the regeneration of damaged myocardium. In order to approach this topic, I have begun with a brief overview of advances in stem cell research in other organ systems, such as the bone marrow and the brain. Very recent progress in cardiac stem cell research is then discussed, which indicates that a cardiomyocyte progenitor cell contributes to cardiomyocyte replacement throughout life. This progenitor cell may reside in the heart itself, or derive from a circulating marrow stem cell.     

Cancer stem cells and therapeutic perspectives

The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Stem cells are defined as cells which are able to both extensively self-renew and differentiate into progenitors. Furthermore, stem cells are also attractive candidates as origin of cancers, as in their long lifespan mutations and epigenetic changes they can increase allowing for increasing evolution toward malignancy. Herein, we discuss the evidences reported in literature on existence of cancer stem cells in several tumors and mechanisms of the extrinsic and intrinsic circuitry controlling stem cell fate as well as their possible connections to cancer. In particular, the review will focus on recent results on conserved Polycomb Group (PcG) gene family, an epigenetic chromatin modifiers involved in cancer development and also in the maintenance of embryonic and adult stem cells. There are two distinct multiprotein PcG complexes identified, Polycomb repressive complex (PRC) 1 and 2. The fact that either PRC1 Bmi1 than PRC2 SU(Z)12 components are implicated in self-renewal stem cells and up-regulated in several kind of human cancer, confirm the importance of (de)regulation of the PcG genes in cancer and stem cell biology. Moreover, Bmi1 and SU(Z)12 are downstream target of Sonic hedgehog (Shh) and Wnt signaling respectively, providing for a connection between epigenetic change regulators (PcG) and developmental-signaling pathways. Finally, potential therapies using inhibitors acting on cancer stem cell population such as cyclopamine, an inhibitor of hedgehog signalling, 6-bromoindirubin-3'-oxime (BIO) which acts on GSK3 and inhibitors of beta-catenin signaling such as exisulind and the tyrosine-kinase inhibitor STI571/Gleevac/imatinib will also discuss.     

Neural stem cells and cell death

Neural stem cells (NSC) undergo apoptotic cell death as an essential component of neural development. Here, we present the results of our studies on the mechanisms by which NSC undergo cell death in response to neurotoxic insults. As experimental models we used primary culture of adult NSC from the subventricular zone of the rat brain, and the neural stem cell line C17.2 initially derived from developing mouse cerebellum. NSC undergo apoptosis in response to staurosporine (0.25 microM) as well as agents inducing oxidative stress such as 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). Exposed cells demonstrate an apoptotic morphology, positive TUNEL staining and phosphatidyl serine exposure as labeled with Annexin V. Using an antibody specific for cytochrome c, we found that cells exposed to staurosporine or DMNQ exhibited diffuse fluorescence throughout the cytosol, implying a release of cytochrome c from the mitochondria. In addition to positive immunoreactivity against the active fragment (p17) of caspase-3, the administration of the pan-caspase inhibitor, zVAD-fmk (40 microM), prevents apoptosis. Both NSC and C17.2 express the Fas receptor, and procaspase-8, but exposure to agonistic Fas mAb (250 ng/ml) fails to induce apoptosis. Pretreatment with cycloheximide or actinomycin D does not influence the cell response to Fas mAb, suggesting that the endogenous inhibitor of caspase-8 FLICE-inhibitory protein (FLIP) is not responsible for the inhibition of the Fas pathway. Thus, it appears that the Fas dependent cell death pathway is not operative in these cells, while the mitochondrial pathway is active and caspase-3 serves as an executioner caspase in the apoptotic machinery. It is known that Fas not only induces apoptosis, but can also deliver growth stimulatory signals through activation of the extracellular-signal regulated kinase (ERK) pathway. The Fas-induced ERK phosphorylation that we detect in C17.2 cells suggests that in NSC Fas may function as a mediator of growth rather than death.