细胞药物的种类及生物学特性——细胞药物连载之一

细胞药物是以不同细胞为基础的用于疾病治疗的制剂、药物或产品的统称,是继放疗、化疗之后又一种临床有效的治疗手段,可实施个性化治疗。细胞药物的种类很多,按其生物学特性可分为传统体细胞、免疫细胞以及各种不同的干细胞等。经体外操作过的细胞群,如肝细胞、胰岛细胞、软骨细胞、树突状细胞、细胞因子诱导的杀伤细胞、淋巴因子激活的杀伤细胞、体外加工的骨髓或造血干细胞和体外处理的肿瘤细胞(瘤苗)等。细胞药物已在一些难治性疾病中得到应用,包括血液系统疾病、心血管系统疾病、消化系统疾病、神经系统疾病、免疫系统疾病和抗衰老等。细胞治疗涉及的细胞种类很多,且不同细胞或不同治疗方法各有特点。运用不同的细胞药物来修复病变细胞,以重建受损的功能细胞和组织,恢复其生物学功能,为细胞丢失或损伤性疾病的防治提供了崭新的思路。     

讲座细胞药物的制备工艺——细胞药物连载之二

细胞药物制备的质量直接关系到细胞治疗的效果。由于细胞治疗所用细胞是具有生物学效应的,细胞药物的制备技术和应用方案具有多样性、复杂性和特殊性,不像一般生物药物那样有统一的制作标准。细胞药物的制备过程主要包括供者筛查、供者检测、采集、加工、分离纯化、储存等,以造血干细胞、间充质干细胞、肝细胞及树突状细胞为例对其进行简要介绍。     

细胞药物的临床应用——细胞药物连载之五

近年来,细胞药物在基础研究领域的成果促进了临床应用。现在细胞药物治疗的疾病种类很多,包括神经系统疾病、自身免疫系统疾病、心血管系统疾病、血液系统疾病、消化系统疾病、下肢缺血、整形美容、抗衰老及抗肿瘤等,涉及的细胞主要有各种干细胞、软骨细胞、肝细胞、DC及CIK细胞等。国内外越来越多的机构和组织开展了细胞治疗的临床研究及应用。     

干细胞生物药物研究进展

胚胎干细胞和成年干细胞经培养能产生更多干细胞也可定向分化成神经细胞、血细胞、肝细胞等特定类型的细胞。其中具有潜能的细胞可用来研究治疗帕金森病、糖尿病和脊髓损伤等疾病的生物药物。     

细胞移植治疗脑瘫的研究现状

小儿脑性瘫痪（简称脑瘫）是目前小儿时期最主要的神经运动功能伤残疾病,且终生存在。尽管有支持性医护。但是目前并没有效治疗的方法。近几年,许多实验室开展了利用干细胞移植治疗脑瘫动物模型的研究,并且报道说人脐血干细胞和间充质干细胞对于脑瘫是有治疗作用的。而神经干细胞也被用于移植治疗脑瘫动物模型,并被证明这些移植的神经干细胞能迁移至受损脑部并分化为神经元。本文就至今已发表的一些细胞移植治疗脑瘫的研究中所用到的细胞种类做一综述。     

科学家首次利用人体皮肤细胞培育出类胚胎干细胞

美国和日本的科学家通过改造人体皮肤细胞，培育出一种外观和作用与胚胎干细胞（ES）非常接近的干细胞。这项技术使得在不使用胚胎或卵母细胞的前提下生产用于疾病研究或治疗的干细胞成为可能，从而避开一直困扰学术界的伦理争论．大大推动了与干细胞有关的疾病疗法研究。     

酪氨酸磷酸酶PRL-3增加胃癌细胞BGC823的SP细胞比例并提高其对化疗药物的耐受性

蛋白酪氨酸磷酸酶PRL-3是近年发现的蛋白酪氨酸磷酸酶家族成员,能促进肿瘤细胞的侵袭、转移及上皮细胞间质转型,提示PRL-3可能在肿瘤发生发展及诱导肿瘤干细胞生成中发挥重要作用.由于侧群(SP)细胞具有许多干细胞的性质,SP细胞分选是目前筛选和分离获得干细胞或前体细胞常用的有效方法.为探讨PRL-3在诱导干细胞生成中的潜在作用,本文在建立过表达PRL-3的人胃癌细胞BGC823的基础上,通过SP分选和CCK-8的方法分析PRL-3对BGC823细胞中SP细胞的比例以及对化疗药物耐受性的影响.结果提示,高表达PRL-3提高BGC823中SP细胞的比例（2.5% vs 9.4%）,同时增加BGC823对化疗药物紫杉醇和顺铂的耐受性（相对于对照细胞,其耐药指数分别为1.75和1.29）.由于SP细胞的产生和细胞耐药性的提高与ABC家族基因表达水平上调密切相关,通过定量 RT-PCR和Western印迹检测发现,PRL-3能上调ABCB1和ABCG2的表达.上述研究结果表明,PRL-3有可能通过上调ABCB1和ABCG2的表达,增加胃癌细胞BGC823的SP细胞比例并增加其对化疗药物的耐受性.     

SP细胞研究进展

SP（side population）胞是细胞群体中极少的一部分,它们可将进入细胞核的荧光染料排出胞外,在荧光显微镜下观察或流式细胞检测时表现为不着色,故称为SP细胞。已发现SP细胞和干细胞具有很多共性,且与肿瘤干细胞很相似。对SP细胞及其性质、分离方法、用途,以及SP细胞与肿瘤干细胞的关系等进行了简要阐述。     

细胞药物的制备工艺——细胞药物 连载之二

细胞药物制备的质量直接关系到细胞治疗的效果。由于细胞治疗所用细胞是具有生物学效应的,细胞药物的制备技术和应用方案具有多样性、复杂性和特殊性,不像一般生物药物那样有统一的制作标准。细胞药物的制备过程主要包括供者筛查、供者检测、采集、加工、分离纯化、储存等,以造血干细胞、间充质干细胞、肝细胞及树突状细胞为例对其进行简要介绍。     

《细胞》：药物使癌症干细胞“改邪归正”

加拿大研究人员日前在学术期刊《细胞》上发表研究报告说。他们在实验中发现,抗精神病药物甲硫达嗪可使癌症干细胞”改邪归正”,成为正常细胞,而药物使用不会对其他正常的人体细胞产生副作用。研究人员称,基于这项研究成果,有望研发出新的癌症治疗药物。     

诱导型多能干细胞iPSc研究现状及其移植治疗帕金森综合症应用前景

诱导多能干细胞(i PS细胞)在小鼠和人上的成功获取,使干细胞领域的研究进入了一个崭新的时代。干细胞研究是再生医学的重要组成部分,研究干细胞的最终目的是应用干细胞治疗疾病,其在疾病模型建立、药物筛选、细胞移植等方面具有极大的应用潜力。i PSCs是由体细胞诱导分化而成的"多能细胞",具备和胚胎干细胞类似的功能,既解决了ESCs的伦理障碍,又为ESCs的获得提供了一条全新的途径,具有重要的理论和应用价值。i PS细胞不仅打破了道德理论的束缚,而且在再生医学、组织工程和药物发现及评价等方面具有积极的价值。神经系统遗传性疾病发病率居各系统遗传病之首,但其发病的分子机制仍不完全清楚,运用体细胞重编程技术建立的疾病特异性诱导多能干细胞模型将有助于揭示神经系统遗传性疾病的发病机理。近几年i PS细胞最新研究成果表明,利用疾病患者i PS细胞模型已逐渐应用于帕金森氏病、老年性痴呆症、脊髓侧索硬化症、脊髓肌肉萎缩症及舞蹈症等5种常见神经性退行性疾病发病机理的研究。本文主要对i PSc的发展历程,避免病毒基因干扰诱导i PS细胞进行的优化,以及干细胞尤其是i PS细胞移植治疗帕金森病等神经系统疾病的现状及应用前景进行系统阐述与论证。     

Application of mesenchymal stem cell exosomes and their drug‐loading systems in acute liver failure

Stem cell exosomes are nanoscale membrane vesicles released from stem cells of various origins that can regulate signal transduction pathways between liver cells, and their functions in intercellular communication have been recognized. Due to their natural substance transport properties and excellent biocompatibility, exosomes can also be used as drug carriers to release a variety of substances, which has great prospects in the treatment of critical and incurable diseases. Different types of stem cell exosomes have been used to study liver diseases. Due to current difficulties in the treatment of acute liver failure (ALF), this review will outline the potential of stem cell exosomes for ALF treatment. Specifically, we reviewed the pathogenesis of acute liver failure and the latest progress in the use of stem cell exosomes in the treatment of ALF, including the role of exosomes in inhibiting the ALF inflammatory response and regulating signal transduction pathways, the advantages of stem cell exosomes and their use as a drug‐loading system, and their pre‐clinical application in the treatment of ALF. Finally, the clinical research status of stem cell therapy for ALF and the current challenges of exosome clinical transformation are summarized.     

The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells

Developing effective drug therapies for arrhythmic diseases is hampered by the fact that the same drug can work well in some individuals but not in others. Human induced pluripotent stem (iPS) cells have been vetted as useful tools for drug screening. However, cardioactive drugs have not been shown to have the same effects on iPS cell-derived human cardiomyocytes as on embryonic stem (ES) cell-derived cardiomyocytes or human cardiomyocytes in a clinical setting. Here we show that current cardioactive drugs affect the beating frequency and contractility of iPS cell-derived cardiomyocytes in much the same way as they do ES cell-derived cardiomyocytes, and the results were compatible with empirical results in the clinic. Thus, human iPS cells could become an attractive tool to investigate the effects of cardioactive drugs at the individual level and to screen for individually tailored drugs against cardiac arrhythmic diseases.     

Stem cells and regenerative medicine

Stem cells have been defined as clonogenic cells that undergo both self-renewal and differentiation to more committed progenitors and functionally specialized mature cells. Of late years, stem cells have been identified in a variety of tissues of an adult body. Depending on the source, they have the potential to form one or more, or even all cell types of an organism. Stem cell research provided some outstanding contributions to our understanding of developmental biology and offered much hope for cell replacement therapies overcoming a variety of diseases. The establishment of human ES cell lines enabled us to generate all tissues we comprise. Recently, excitement has been evoked by the controversial evidence that adult stem cells have a much higher degree of developmental plasticity than previously imagined. More recently, the existence of multipotent somatic stem cells in bone marrow has been reported. Combined with these discoveries and achievements as well as the developing technologies, scientists are now trying to bring stem cell therapies to the clinic.     

Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways

Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.     

诱导多能干细胞及其在神经退行性疾病研究中的应用

用干细胞转录因子OCT4、SOX2、c-MYC和KLF4进行体细胞重编程产生具有胚胎干细胞特性的诱导多能干细胞(iPS细胞)是干细胞研究领域的突破性进展。近年来,iPS细胞的研究从产生方法、重编程机理及实际应用方面不断取得进展。由于iPS细胞的产生可取自体细胞,因而克服了胚胎干细胞应用的伦理学和免疫排斥等缺陷,为iPS细胞的临床应用开辟了广阔的前景。该文将对iPS细胞的产生方法、重编程机理及其在神经性退行性疾病的研究与应用进行文献综述,反映近几年iPS细胞最新研究成果,并阐述了用病人iPS细胞模型探讨帕金森氏病、老年性痴呆症、脊髓侧索硬化症、脊髓肌肉萎缩症及舞蹈症等5种常见神经性退行性疾病发病机理的研究现状。