干细胞的应用研究现状

目前医学发展的两个重要方面,一是分子生物学领域的基因工程,另一方面是与移植和再造有关的细胞组织工程。前者在省、市级科研和医疗单位难以跟踪,而在组织工程方面却可通过努力大有作为。以胚胎干细胞研究为例,胚胎干细胞是尚未分化成各种组织和器官的原始细胞,它具有发育分化成组织器官细胞的潜力。胚胎干细胞移植与其它生物技术联合应用在未来几年很可能在移植领域引发革命性进步。目前,人们在     

全能干细胞的研究现状与前景

干细胞是具有全能或多能分化潜能（胚胎干细胞ES，EG）和广泛存在于成体器官组织中保留不分化和维持身体自我更新能力（组织干细胞）的特种细胞。由于这种细胞的高度可塑性和在组织修复、疾病的细胞治疗以及生殖遗传工程等方面的潜在应用价值，近年来成为生命科学研究领域中最热点的课题之一。     

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。     

体外诱导人胚胎干细胞向神经细胞分化的研究进展

研究表明胚胎干细胞（embryonic stemcells,ES细胞）在体外可以发育分化出神经组织细胞,这对于了解神经发育的机制和研究神经组织退化性或脑组织损伤性疾病的治疗具有重要的意义。本文就胚胎干细胞分化为神经组织细胞的常用方法和机制做一综述。     

胚胎干细胞体外分化为肝细胞和心肌细胞的研究进展

胚胎干细胞是从早期胚胎或原始性腺分离后能在体外长期传代培养的全能细胞系。胚胎干细胞体外可以诱导分化为各种体细胞,并且用这些体细胞治疗相应的疾病,一直以来是生物医药领域的研究焦点。目前,在该领域用于诱导胚胎干细胞分化的方法很多,其中的一些方法就用到化合物和部分中药提取物。整理近5年来胚胎干细胞体外通过拟胚体途径、细胞单层诱导分化为肝细胞和心肌细胞的有关文献,做一简要综述。     

干细胞在眼科的研究进展

近年来,以干细胞为核心的组织工程学研究标志着再生医学时代的到来。干细胞在眼科领域的应用研究也取得了长足进展。胚胎干细胞和成体干细胞在受损眼表修复重建和各种视网膜疾病的治疗研究中都具备巨大的潜力。干细胞与组织工程的结合为解决目前眼科发展面临的问题提供了丰富的材料来源和崭新的探索思路。     

造血干细胞移植术的研究进展

干细胞是指尚未分化的细胞,是一类具有自我更新、高度增殖和多向分化潜能的细胞群体,存在于早期胚胎、骨髓、脐带、胎盘和部分成年人细胞中,它通过分化能够产生某一组织的一种或多种特定的细胞群体,如被培育成肌肉、骨骼和神经等人体组织和器官;     

诱导间充质干细胞向心肌细胞分化方法及分化机制进展

干细胞在体外特定条件下,可特异的向某种组织类型细胞进行分化,其中包括向心肌细胞分化。目前,胚胎干细胞(em-bryonic stem cells,ESCs)虽然具有这方面的功能,且其分化效率较一般成体细胞高,但是由于伦理问题限制了其在临床的应用。而间充质干细胞(mesenchymal stem cells,MSCs)不仅取材方便,且没有伦理争议,是最具希望的再生医学种子细胞,引起了人们的极大关注。目前对于体外诱导不同来源的间充质干细胞向心肌细胞分化方法的实验研究很多,主要包括化学试剂诱导和模拟体内微环境诱导两大类。该文就MSCs向心肌分化的体外诱导方法和分化机制的研究进展作一综述。     

干细胞治疗基础及应用

各种疾病导致的组织器官病理损伤和功能障碍是人类健康的主要危害,传统治疗方法效果往往不能尽如人意.基础研究显示,干细胞具有分化为多种细胞的潜能,干细胞移植具有促进细胞因子分泌、改善微循环、对抗凋亡等作用.用干细胞技术来治疗各种组织损伤性疾病为克服传统治疗的不足提供了一种新的技术手段.     

自体脐血干细胞采集临床资料分析

干细胞是具有自我复制和分化潜能的原始细胞,是机体的起源细胞,能形成人体各种组织器官。干细胞可来自骨髓、外周血、脐血及胚胎,而脐血中干细胞含量丰富,也最易获得。我们自2002年10月以来对4例孕妇进行了自体脐血干细胞采集,现就有关资料分析介绍如下。     

The effect of plant phenols on the expression and activity of phorbol ester-induced PKC in mouse epidermis

During early embryonic development, at blastocyst stage, the embryo has an outer coat of cells and an inner cell mass (ICM). ICM is the reservoir of embryonic stem (ES) cells, which are pluripotent, i.e., have the potential to differentiate into all cell types of the body. Cell lines have been developed from ES cells. In addition, there are embryonic germ (EG) cell lines developed from progenitor germ cells, and embryonic carcinoma (EC) cell lines developed from teratomas. These cell lines are being used for the study of basic and applied aspects in medical therapeutics, and disease management. Another potential of these cell lines is in the field of environmental mutagenesis. In addition to ES cells, there are adult stem cells in and around different organs and tissues of the body. It is now possible to grow pure populations of specific cell types from these adult stem cells. Treating specific cell types with chemical or physical agents and measuring their response offers a shortcut to test the toxicity in various organ systems in the adult organism. For example, to evaluate the genotoxicity of a chemical (e.g., drug or pesticide) or a physical agent (e.g., ionizing radiation or non-ionizing electromagnetic radiation) during embryonic development, a large number of animals are being used. As an alternative, use of stem cell lines would be a feasible proposition. Using stem cell lines, efforts are being made to standardize the protocols, which will not only be useful in testing the toxicity of a chemical or a physical agent, but also in the field of drug development, environmental mutagenesis, biomonitoring and other studies.     

生物活性因子修饰骨髓间充质干细胞的研究进展

骨髓间充质干细胞（BMSCs）是骨髓基质中存在的非造血系的具有多向分化潜能的成体干细胞,现已成为国内外医学研究的热点。生物活性因子分布在人体各个组织中,对骨髓间充质干细胞具有重要的调节作用。文章从BMSCs的含义、细胞特性、联合多种生物活性因子及对组织的治疗等方面进行详细的阐述。     

正常肺及肺腺癌组织中细支气管肺泡干细胞相关指标的表达

目的检测人正常肺及肺腺癌组织中细支气管肺泡干细胞（BASC）相关指标,明确BASC是否在人肺组织中存在及其组织定位。方法采用组织免疫荧光方法将经过脱蜡、抗原修复好的组织切片通过5％脱脂奶粉溶液封闭检测,再通过先后加入一抗、二抗以及染核、封片等在荧光显微镜下观察,判定结果时可见合成蛋白复合物（SPC）和八聚体结合转录因子4（OCT4）阳性表达细胞呈绿色,Clara细胞分泌蛋白（CCSP）阳性表达细胞呈红色,而SPC／CCSP或CCSP／OCT4双阳性细胞呈黄色,细胞核呈蓝色。结果在人正常肺组织中可检测到SPC、CCSP及OCT4。免疫荧光检测显示,正常肺组织中均可检测到SPC、CCSP双阳性表达细胞,呈现BASC的表型特征,且均表达OCT4,定位于细支气管一肺泡导管连接处。在人肺腺癌组织中亦可检测到BASC样癌干细胞,在30例肺腺癌组织中26例同时检测出SPC及CCSP,属检测出BASC病例。18例同时检测出OCT4表达。结论人正常肺组织中可检测到BASC,且在肺腺癌组织中可检测到具有BASC表型特征的癌干细胞,提示人肺腺癌可能源自BASC的恶性转化。     

Stem cell-derived hepatocytes and their use in toxicology

Better prediction of safety risk and understanding of mechanism of action of drug candidates remain a major challenge in order to prevent late stage attrition. Continuous efforts are made to improve and develop new models, especially in some areas such as hepatotoxicity. Besides primary hepatocytes and transformed liver cell lines, stem cells either isolated from embryos or adult tissues or obtained by reprogramming somatic cells are emerging as a new potential source of unlimited numbers of hepatocytes. Presently, only hepatocyte-like cells expressing low levels of liver-specific markers, especially drug metabolizing and detoxifying enzymes, are usually obtained, making them still unsuitable as metabolically competent cells for toxicity studies. The only exceptions are some hepatoma cell lines, particularly the HepaRG cell line that can differentiate from a bipotent progenitor stage to attain the functional capacity of normal adult hepatocytes in primary culture without losing the indefinite growth property of transformed cells. Since the research field on stem cells is growing fast marked advances might be expected in the next future.     

Very small embryonic-like stem cells for regenerative medicine: WO2010039241

Background: The application is in the field of stem cells and regenerative medicine.

Objective: It aims at identifying and characterising a population of pluripotent stem cells present in adult tissues.

Methods: Cells were isolated and purified using Fluorescence-Activated Cell Sorting and Direct ImageStream analysis from various adult and umbilical cord tissues of rodents and humans. Cells were propagated in the presence of trophic factors and feeder cell layers of C2C12 cells. Cells were characterised by electron microscopy and immunocytology.

Results: A population of cells that do not express a panleukocytic antigen CD45 and are negative for other markers of haematopoietic lineages were isolated and purified. The isolated cells elicit morphological features of embryonic stem cells (ESCs). They express markers of pluripotent stem cells, such as Nanog, Oct-4 and SSEA-1. On culturing on feeder cell layers, the isolated and purified cells generate embryoid body-like sphere.

Conclusion: The identified and characterised cells elicit features of pluripotent stem cells and similarities with ESCs. They are termed very small embryonic-like stem cells (VSELs). The application claims the use of VSELs for cellular therapy and regenerative medicine.     

干细胞临床研究及管理的现状与未来

干细胞研究和临床试验发展迅速,目前全球干细胞临床研究排名前三的国家或地区分别是美国、欧洲和中国,干细胞治疗种类以造血干细胞为主,间充质干细胞日益增长,神经干细胞和多能干细胞的临床试验也相对较多。目前全球已有14款干细胞药物上市,超过一半以上是间充质干细胞治疗产品。中国共有87个干细胞临床项目完成备案,其中间充质干细胞备案项目最多。细胞治疗是按照医疗技术还是药品来监管,世界各国有所不同。在美国按细胞组织类产品风险高低进行归类监管,欧盟以先进技术治疗医学产品归类监管,日本按照再生医学产品管理,中国目前进行机构和项目双备案制度。在严格分类管理的基础上,无论欧盟的医院豁免制度、日本的条件限制性准入政策,还是中国从药品-第三类医疗技术-备案制管理政策的变迁,都为干细胞及其他细胞治疗产品的研究和应用提供了科学而快速发展的政策保障。对国内外干细胞临床研究及应用的发展现状进行综述,同时分析各国干细胞临床研究相关的法律法规与质量控制监管政策。     

Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow,heart,liver,muscle,lung,derma,kidney,and fat

Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1⁺CD34⁻ postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level in vitro, and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1⁺CD34⁻ PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1⁺CD34⁻ PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the “stem cell plasticity” found in multiple human tissues. In addition, as fetal BM-derived Flk1 + CD34⁻ PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings in vitro. Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.     

干细胞样SP细胞研究进展

摘要： 干细胞样 SP 细胞是近年来在很多正常组织和恶性肿瘤组织及细胞系中发现的一种具有不同程度分化潜能和自我更新能力的细胞群体。虽然 SP 细胞在总体细胞中所占比例很低, 但这部分具有干细胞特性的细胞在干细胞以及肿瘤干细胞研究方面起着越来越重要的作用。本文综述了 SP 细胞的发现、 生物学特性、 与肿瘤干细胞之间的关系以及 SP 细胞的未来临床应用等。最后对 SP 细胞的发展进行了展望。     

间充质干细胞成骨和成脂分化调控机制研究

间充质干细胞（MSCs）是人体内参与免疫平衡、维持组织器官的稳态和功能以及组织损伤修复的一类重要成体干细胞。MSCs具有自我更新能力和多向分化潜能,国际干细胞协会将MSCs向脂肪、成骨等细胞分化的能力作为其重要的检测标准。作为骨细胞和脂肪细胞的共同来源,MSCs在成骨和成脂分化之间相互协调和相互竞争,并在多种调控因素作用下保持着微妙的平衡。对MSCs成骨、成脂分化的信号通路、调控因素进行分析,并对其分化诱导方法以及鉴定方法进行总结,以期为MSCs基础研究及临床应用提供参考依据。     

基因修饰间充质干细胞治疗肿瘤研究进展

间充质干细胞（MSCs）是来源于中胚层的成体干细胞,体内分布广泛,可从骨髓、脂肪、牙髓、脐带/胎盘等组织中分离获取,具有高度的可增殖和分化潜能,较低的免疫原性,同时具有向炎症损伤部位微环境的趋向性,在疾病治疗方面可作为基因药物的载体实现精准治疗。癌症被认为是永远无法愈合的伤口,其组织微环境在损伤与修复中呈无休止的动态变化,MSCs在其中扮演了重要角色。利用MSCs具有的向肿瘤组织中归巢及定位的特点,对其进行抗肿瘤药物的基因工程改造可能在癌症的治疗上是一种新的策略。概述MSCs在癌症发生发展中的作用以及基因修饰MSCs治疗癌症的研究进展,旨在为临床使用基因修饰MSCs治疗癌症提供策略和见解。