空间代谢组学在肿瘤中的应用及前景

空间代谢组学是基于质谱成像技术, 对组织中代谢物的种类、含量、空间分布差异进行分析, 具有无需标记、免基质、灵敏度高的特点, 相比传统代谢组学增加了对空间信息的研究。本文介绍代谢组学和质谱成像技术以及它们的研究现状, 重点综述空间代谢组学在肿瘤各个领域的应用, 介绍了空间代谢组学技术的现有瓶颈并展望了其未来发展方向。     

代谢组学技术在烧伤领域的应用研究进展

代谢异常是烧伤最基本的病理生理特征,持久而顽固的高代谢反应是危重烧伤患者最显著的代谢特征。代谢组学对生物体在受到病理生理上的刺激以及某种基因修饰所带来的代谢物的动态变化进行研究,进而探寻对疾病诊治有重要价值的生物标志物,为伤情评估、疗效判断、个性化用药提供新的客观依据。近年来,代谢组学在烧伤诊治方面的应用也日益成为研究热点。本文就代谢组学及代谢组学技术在烧伤领域应用等方面的研究进展进行综述。     

干细胞移植治疗中的示踪术研究现状(文献综述)

示踪术是指利用放射性核素及其标记化合物或者其它带有特定检测标志的物质进入生物体内 ,对体内各种代谢物质的吸收、分布、转移规律、疾病进行诊断研究的一门科学。其在医学生物学各学科应用非常广泛。干细胞移植是一种可能治愈各种缺陷性疾病有效的治疗手段[1] ;但是不论何种干细胞移植后观察其治疗机制如分化、迁移、存活、体内分布等各种医学证据都离不开示踪技术 ,各种干细胞种类不同 ,其生物学特性不同 ,进行示踪的手段和灵敏度也会不同。为此 ,将干细胞移植中的各种示踪技术综述如下。1　核素在干细胞移植中的示踪研究1935年 ,Heves…     

干细胞治疗肝硬化的研究进展

干细胞是指那些具有长期自我更新和产生至少一种终末分化细胞能力的细胞.干细胞移植可用来治疗的肝脏疾病如急性肝衰竭、遗传性代谢性肝疾病以及终末期肝疾病等,成为当前研究的热点。综述了,近年来用于治疗肝脏疾病的干细胞种类、干细胞的示踪以及干细胞的临床应用研究现状及进展,并对干细胞用于治疗肝硬化存在的一些问题以及今后的研究重点作了简要分析。     

胚胎干细胞定向诱导分化为心肌细胞进展

在个体发育过程中，通常把那些具有自我复制能力并能在一定条件下分化形成一种以上类型细胞的多潜能细胞称为干细胞。根据其发育阶段，干细胞可分为胚胎干细胞和成体干细胞。由于胚胎干细胞具有在体外培养下保持未分化状态的增殖能力及分化为多种细胞类型的潜能，使之成为一种研究哺乳动物细胞分化、组织形成过程的基本体系，以及临床移植治疗的新的细胞来源。人们利用胚胎干细胞建立了各种体外分化模型，本文将概述现今对胚胎干细胞定向诱导分化为心肌细胞方面的主要进展和趋势。     

融合基因表达差异的生物代谢变化预测

目的当前存在许多基于约束的优化建模方法利用全基因组的代谢网络来预测生物代谢流量分布,而几乎所有的这些建模方法都需要代谢物的摄取和分泌速率以及生物先验知识的信息,比如假设生物量或者ATP产量最大。但是由于多细胞生物代谢物的摄取和分泌速率的测量很困难,并且多细胞高等生物的不同组织通常有不同的代谢目标,所以很难确定一个合理的代谢目标来建模研究高等生物的代谢。本文利用基因表达的差异信息和代谢网络,能够预测单细胞或多细胞生物代谢流量的变化,不需要生物的先验知识和代谢物分泌或摄取速率的信息。方法模型假设在两点状态下,如果编码酶的基因表达量存在显著变化,则酶催化的反应的代谢流量也应该存在显著变化。利用微阵列基因组学数据和生物全基因组的代谢网络,通过使生物代谢流量的变化与基因表达的变化尽可能一致来建立优化模型,预测生物显著差异的代谢流量分布。结果模型利用在有氧恒化器中以不同稀释速率生长的大肠杆菌的基因表达数据,预测的代谢流量与实验中实际测量的代谢流量一致。结论本文提出的基于约束的建模方法可以简单准确地定性预测低等生物的代谢流量变化,为研究高等生物的代谢变化提供了有效途径。     

骨髓间充质干细胞在1型糖尿病治疗中的应用

骨髓间充质干细胞是一种既具有自我更新能力又有多向分化潜能的细胞,研究显示骨髓间充质干细胞将可用于许多疾病的治疗,如心肌坏死、肝功能衰竭、1型糖尿病等.本文概述了骨髓间充质干细胞研究现状,结合现阶段糖尿病治疗进展并比较其它方法的治疗效果,阐述了骨髓间充质干细胞在治疗1型糖尿病中的运用前景.     

不同类型干细胞在心肌组织工程中的应用及进展

慢性缺血性心脏病多由冠状动脉粥样硬化引起,目前治疗上较为棘手.近年来,心肌组织工程的发展为此疾病的治疗带来了曙光.心肌组织工程主要包括种子细胞的获取、支架材料的研制、以及心肌组织的构建三部分.种子细胞的来源和种类则是心肌组织工程中的关键环节.我们总结近年来干细胞研究的进展,对研究较多的几种干细胞在心肌组织工程中的应用作一综述,这些干细胞包括:心脏祖细胞,胚胎干细胞,间充质干细胞,诱导多能干细胞,以及用于构建心肌再生的内皮祖细胞等,并对未来干细胞的发展作一展望.     

创伤性脊髓损伤患者血清和尿液的代谢组学分析

背景:创伤性脊髓损伤在临床上主要依赖于量表评估与影像学检查,但对于损伤程度的预后评估具有一定局限性,利用代谢组学技术进行生物标志物筛选,对于估计病变范围、损伤与恢复程度以及开发新疗法具有重要意义。目的:使用代谢组学技术来表征创伤性脊髓损伤患者的代谢特征,探寻潜在的生物标志物及失调的代谢途径。方法:收集20例创伤性脊髓损伤患者(观察组)和10例健康受试者(对照组)的血清和尿液样本,进行代谢物分析,然后利用多元变量统计分析进行数据处理,筛选差异代谢物。通过MetaboAnalyst软件进行代谢通路富集,应用logistic回归构建生物标志物组合模型,并分析其与美国脊髓损伤协会(ASIA)分级的关系。结果与结论:两组受试者的血清和尿液中分别检测出160种和73种具有显著差异的代谢物。通路富集分析显示,创伤性脊髓损伤后脂质代谢出现明显的紊乱,包括鞘脂类、亚油酸、α-亚麻酸和花生四烯酸代谢以及糖基磷脂酰肌醇生物合成。识别出他索沙坦和葫芦素糖苷这组生物标志物,并且二者构成的代谢物组合在血清和尿液中的水平与ASIA分级存在相关性。由此可见,代谢组学技术为进一步理解创伤性脊髓损伤病理机制、筛选治疗靶点提供帮助。识别出的代谢生物标志物组合可能为评估创伤性脊髓损伤的严重程度提供参考。     

基于代谢组学评价血液生物标志物对中枢神经系统肿瘤的诊断价值

目的 分析中枢神经系统肿瘤代谢组学图谱,评价小分子代谢物作为中枢神经系统肿瘤生物标志物的诊断价值.方法 本研究纳入126例中枢神经系统肿瘤患者和86例健康对照人群.通过液相色谱质谱联用技术(LC-MS/MS)检测血液中氨基酸和酰基肉碱,分析中枢神经系统肿瘤代谢组学图谱.用ROC曲线对小分子代谢物进行诊断效能分析.结果 中枢神经系统肿瘤代谢谱与健康人群有明显区别,19个指标有显著差异.肿瘤患者血液C2水平显著低于健康人群.Arg,C8和C18:2对中枢神经系统原发性肿瘤具有辅助诊断价值,ROC曲线下面积分别为0.868、0.895和0.756,灵敏度分别为82.6%、88.0%和60.9%,特异性分别为77.5%、80.8%和78.3%.结论 血液中小分子代谢物,包括氨基酸和酰基肉碱可作为中枢神经系统肿瘤辅助诊断新的生物标志物.     

活性氧在多能干细胞中的作用

Pluripotent stem cells are characterized by the properties of self-renewal and the ability to differentiate into multiple cell types. Reactive oxygen species (ROS) are highly reactive metabolites. High levels of ROS are toxic and involved in stem cell senescence and apoptosis. However, regulation of ROS has an important role in maintaining “stemness” and differentiation of the stem cells. The role of ROS in the stem cells varies among different stem cell types. NADPH oxidase is one of the major sources of ROS in stem cells. Excessive amounts of ROS are produced in various pathophysiological states such as atherosclerosis, heart failure, hypertension, diabetes, and aging. Induced pluripotent stem cells have the potential to be used in modeling of ROS-associated diseases.Understanding the molecular mechanisms  how ROS regulate the functions of stem cells will greatly enhance their translational applications. In this review, we summarize the recent progress regarding the roles of ROS in regulating the functions of embryonic and induced pluripotent stem cells.     

Smooth muscle and other cell sources for human blood vessel engineering

Despite substantial progress in the field of vascular tissue engineering over the past decades, transition to human models has been rather challenging. The limited replicative life spans of human adult vascular cells, and their slow rate of collagenous matrix production in vitro, have posed important hurdles in the development of mechanically robust and biologically functional engineered grafts. With the more recent advances in the field of stem cells, investigators now have access to a plethora of new cell source alternatives for vascular engineering. In this paper, we review various alternative cell sources made available more recently for blood vessel engineering and also present some recent data on the derivation of smooth muscle cells from human induced pluripotent stem cells.     

干细胞：代谢综合征治疗的新资源

背景：代谢综合征是以糖、脂等代谢紊乱及向心性肥胖、高血压为特征的系列症候群,传统的治疗尚不能从根本上改善、治愈代谢综合征。 目的：综述干细胞移植治疗代谢综合征的研究进展,并提出干细胞使用方面许多亟待解决的问题。 方法：使用计算机检索Pubmed数据库及中国学术期刊全文数据库(CNKI)2002至2011年有关干细胞移植治疗代谢综合征胰岛素抵抗、高血糖、高血脂、高血压等组分的研究文献。英文检索词为“stem cells,metabolic syndrome,insulin resistance,diabetes,hyperlipidemia,hypertension,stem cells transplantation”,中文检索词为“干细胞、代谢综合征、胰岛素抵抗、糖尿病、高脂血症、高血压、干细胞移植”。排除陈旧性和重复性研究,收集到43篇相关文献纳入综述。 结果与结论：干细胞是机体组织细胞的起源,具有自我复制、高度增值和多向分化的能力,干细胞治疗可促进各种损伤修复和衰老死亡细胞的更新,从而改善组织器官的结构与功能,促进代谢产物的利用及排泄。相关研究证实干细胞可通过各种机制治疗代谢综合征的脂代谢紊乱、胰岛素抵抗、高血压、高血糖、动脉粥样硬化等病变。关于干细胞移植治疗代谢综合征,目前还有很多尚待解决的问题,但现有研究资料已经证实,干细胞移植治疗代谢综合征是一个充满希望的新途径。     

Neural stem cells: plasticity and their transdifferentiation potential

The presence of resident stem cells in adult tissues is of fundamental importance for the maintenance of their structural and functional integrity. In fact, throughout life, somatic stem cells attend to the critical function of substituting terminally differentiated cells lost to physiological turnover, injury or disease. Thence, one of the basic dogmata in tissue biology holds that the differentiation potential of an adult stem cell is restricted to the generation of the mature cell lineages found in the tissue to which the stem cell belongs. A plethora of recent evidences from many groups, including ours, is now providing evidence that adult stem cells may possess a broader differentiation repertoire than expected and that their fate potential may not be as tissue specific as once thought. The initial example of an unforeseen, trans-germ layer plasticity - that seems now to emerge as a prototypic functional trait of various somatic stem cells of different origin - has come from the reported awakening of a latent hemopoietic developmental capacity in stem cells isolated from the adult mammalian brain following their transplantation into sub-lethally irradiated mice. More recently, it has been shown that adult neural stem cells can differentiate into a wide array of bodily cells of different origin when injected into the blastocyst and into myogenic cells when transplanted into the adult regenerating skeletal muscle. Moreover, bone marrow stem cells can now give rise to skeletal muscle, hepatic and brain cells, whereas muscle precursors can generate blood cells. In this article, we review some of the basic notions regarding the functional properties of the adult neural stem cells and discuss findings in the expanding area of trans-germ layer conversion, with emphasis on the neural stem cell.     

The iPS Technique Provides Hope for Parkinson’s Disease Treatment

More recently, reprogramming of somatic cells to an embryonic stem cell-like state presents a milestone in the realm of stem cells, making it possible to derive all cell types from any patients bearing specific genetic mutations. With the development of induced pluripotent stem (iPS) cells, we are now able to use the derivatives of iPS cells to study the mechanisms of disease and to perform drug screening and toxicology testing. In addition, differentiated iPS cells are now close to be used in clinical practice. Here we review the progress of iPS technique and the possible application in the area of Parkinson’s disease treatment.     

A challenge for regenerative medicine: proper genetic programming, not cellular mimicry.

Recent progress in stem cell biology and the reprogramming of somatic cells to a pluripotent phenotype has generated a new wave of excitement in regenerative medicine. Nonetheless, efforts aimed at understanding transdifferentiation, dedifferentiation, and the plasticity of cells, as well as the ability of somatic cells to be reprogrammed, has raised as many questions as those that have been answered. This review proffers the argument that many reports of transdifferentiation, dedifferentiation, and unexpected stem cell plasticity may be due to aberrant processes that lead to cellular look-alikes (cellular mimicry). In most cases, cellular look-alikes can now be identified readily by monitoring gene expression profiles, as well as epigenetic modifications of DNA and histone proteins of the cells involved. This review further argues that progress in regenerative medicine will be significantly hampered by failing to address the issue of cellular look-alikes.     

组织工程种子细胞的研究进展

组织工程学近年来研究进展很快 ,目前采用组织工程技术建造的部分组织或器官已经开始进入或即将进入临床应用 ,如组织工程化皮肤已经实现商品化 ,软骨组织工程产品也已经进入临床前期实验阶段 ,在近年内即可进入临床应用[1～ 3 ,12 ] 。组织工程研究成功与否主要取决于以下三个关键性制约因素 :种子细胞、支架材料以及有助于细胞生长、分化的外在环境。其中获得足够数量、不引起免疫排斥反应且具有再生活力的种子细胞是开展组织工程研究的前提和基础。尽管目前种子细胞的研究仍面临众多挑战 ,但令人欣喜的是 ,随着干细胞体外分离、培养和扩…     

骨髓间充质干细胞诱导成肌的研究进展

骨髓间充质干细胞(MSCs)是一种取材方便,易于培养的多能干细胞,研究者一直在探索MSCs向肌源性细胞诱导分化的方法,通过生物化学诱导、生物力学刺激诱导等多种方法可使MSCs向肌细胞分化,应用于临床,治疗缺血性心肌病及肌组织创伤后的修复。就目前MSCs诱导成肌方面的研究以及MSCs的分离、纯化及鉴定作一综述。     

The role of stem cells in physiology, pathophysiology, and therapy of the liver

The objectives of the present review is to update readers with the rapidly changing concepts in liver stem cell biology and related clinical applications. The liver has adapted to the inflow of ingested toxins by the evolutionary development of unique regenerative properties and responds to injury or tissue loss by rapid division of the mature cells, hepatocytes, and bile duct epithelial cells. Proliferation of the parenchymal cells is regulated by numerous cytokine/growth factor-mediated pathways and is timely synchronized with extracellular matrix degradation and the restoration of the vasculature. The putative role of stem cells in physiology, pathophysiology, and therapy is not yet precisely known but currently is under intensive investigation. Resident hepatic stem/ progenitor cells have been identified in small numbers and implicated in liver tissue repair, when hepatocyte and bile duct replication capacity is exhausted or experimentally inhibited. Several independent reports have suggested that bone marrow cells can give rise to different hepatic epithelial cells types, including hepatic stem cells, hepatocytes, and bile duct epithelium. These observations have resulted in the hypothesis that extrahepatic stem cells, specifically bone marrow-derived stem cells, are an important source for liver epithelial cell replacement, particularly during chronic injury. Most of published data, however, now suggest that they do not play a relevant role in replacement of epithelial cells in any known form of hepatic injury. In vitro differentiation protocols for various adult extrahepatic stem cells might eventually provide valuable sources of cells for transplantation and therapy. Amniotic epithelial stem cells, fetal liver progenitor cells as well as embryonic stem cells currently emerge as alternative stem cell sources and open new possibilities for cellular therapies of liver disease.     

The Advancement of Biomaterials in Regulating Stem Cell Fate

Stem cells are well-known to have prominent roles in tissue engineering applications. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into every cell type in the body while adult stem cells such as mesenchymal stem cells (MSCs) can be isolated from various sources. Nevertheless, an utmost limitation in harnessing stem cells for tissue engineering is the supply of cells. The advances in biomaterial technology allows the establishment of ex vivo expansion systems to overcome this bottleneck. The progress of various scaffold fabrication could direct stem cell fate decisions including cell proliferation and differentiation into specific lineages in vitro. Stem cell biology and biomaterial technology promote synergistic effect on stem cell-based regenerative therapies. Therefore, understanding the interaction of stem cell and biomaterials would allow the designation of new biomaterials for future clinical therapeutic applications for tissue regeneration. This review focuses mainly on the advances of natural and synthetic biomaterials in regulating stem cell fate decisions. We have also briefly discussed how biological and biophysical properties of biomaterials including wettability, chemical functionality, biodegradability and stiffness play their roles.