诱导多能干细胞向巨噬细胞分化研究进展

诱导多能干细胞 (Induced pluripotent stem cells,iPSCs) 是通过体细胞重编程得到类似胚胎干细胞特性的一种细胞类型。通过iPSCs的体外分化,可以了解巨噬细胞的进化历史和各种特性。iPSCs来源的巨噬细胞不仅是药物筛选的良好模型,也是进行免疫治疗的重要手段。本文综述了近年来iPSCs及其向巨噬细胞分化的相关研究进展、所面临的问题以及未来的发展方向。     

多能干细胞诱导分化为肾脏类器官的分子机制及应用前景分析

干细胞具有自我更新和多向分化潜能,在再生医学领域发挥着越来越大的作用。肾脏类器官是一种由干细胞分化而来具有一定肾脏功能的组织结构,可用于肾脏疾病的细胞修复治疗,也可以模拟肾脏发育和疾病发生及用于筛选改善肾功能的药物。肾脏类器官的体外培育成为了当前研究热点,其体外培育可分为几个阶段：干细胞-原始体节中胚层-中间中胚层-输尿管芽（后肾间质）-集合管（肾单位）。本文重点介绍了目前两种较为成熟的肾脏类器官体外诱导方法,并对肾脏类器官的应用前景进行了综述。     

多能干细胞诱导分化为肾脏类器官的研究进展与挑战

用于分化为多种类型细胞的多能干细胞(PSC)体外培养技术已被广泛应用于生物学领域中.由PSC分化而来的肾脏类器官可基本还原生物体内肾脏的组织结构和部分功能,在肾脏疾病模型研究和药物筛选中有重要作用,继续改善肾脏类器官的结构、功能和成熟度将会对肾脏再生治疗提供极大的帮助.研究肾脏类器官的重点在于体外准确模拟体内肾脏的发育...     

猪多能干细胞的研究进展

多能干细胞,如胚胎干细胞(embryonic stem cells,ESCs)、诱导多能干细胞(induced pluripotent stem cells,iPSCs)和成体干细胞(adult stem cells,ASCs),是一类具有巨大潜能的独特细胞。猪作为试验材料,在遗传、代谢、生理生化及基因序列等方面较小鼠更接近于人类,正逐渐成为人类异种移植和再生医学研究的理想生物学模型。然而,目前对猪多能干细胞种类、来源、特征及机制的有限认识直接阻碍了其相关应用。该文将分别对猪ASCs的研究现状、猪类ESCs的分离培养、猪iPSCs的研究进展、多能干细胞间的联系和展望进行论述,以期为从事该领域研究的科研人员提供参考。     

猪多能干细胞的研究进展

多能干细胞,如胚胎干细胞（embryonic stem cells,ESCs）、诱导多能干细胞（induced pluripotent stem cells,iPSCs）和成体干细胞（adultstemcells,ASCs）,是一类具有巨大潜能的独特细胞。猪作为试验材料,在遗传、代谢、生理生化及基因序列等方面较小鼠更接近于人类,正逐渐成为人类异种移植和再生医学研究的理想生物学模型。然而,目前对猪多能干细胞种类、来源、特征及机制的有限认识直接阻碍了其相关应用。该文将分别对猪ASCs的研究现状、猪类ESCs的分离培养、猪iPSCs的研究进展、多能干细胞间的联系和展望进行论述,以期为从事该领域研究的科研人员提供参考。     

诱导多能干细胞研究进展

人类诱导多能干细胞（induced pluripotent stem cells,iPS细胞）的建立被公认为目前最重要的科技进展之一。iPS细胞在动物疾病模型上的成功治疗,病患特异性iPS细胞的研究及iPS细胞的定向分化研究将有可能使人们避开治疗性克隆的伦理和技术障碍,给人类疾病的干细胞治疗带来光明的前景。本文从iPS细胞的诱导策略和方法,来源细胞及筛选、重编程机制的研究现状、应用前景以及研究中存在的问题等方面对其作一综述和讨论。     

多能干细胞向雄性生殖细胞定向分化的研究进展

生殖健康是生命科学领域关注的核心之一,各种原因所致男性不育亟待解决,然而由于伦理限制等原因,缺少合适的具有人类遗传背景的研究模型开展研究。胚胎干细胞（ESCs）和诱导多能干细胞（iPSCs）均属于多能干细胞,具有多向分化潜能。一方面,可利用ESCs?/?iPSCs向生殖细胞分化的模型研究人类生殖细胞的发育规律,另一方面,在此基础上,可建立带有人类疾病遗传背景的iPSCs模型,体外诱导其向雄性生殖细胞分化,利用该模型研究男性不育的发病机制。由于精子在体内的形成遵循一定规律,体外环境中不同发育阶段的生殖细胞在不同诱导因子作用下才可稳定地往下一阶段定向分化,因此,诱导ESCs?/?iPSCs向雄性生殖细胞方向分化时,诱导因子的种类和加入时间的选择应根据生殖细胞的体内发育特征而定,并且在诱导的不同阶段循序加入,以此模拟精子在体内的形成过程,进而更好地研究男性不育的发病机制。本文将对多能干细胞向雄性生殖细胞定向分化的常用诱导因子及存在问题和展望进行综述,为相关研究的开展提供借鉴。     

新物种诱导多能干细胞的研究进展

胚胎干细胞（embryonic stem cells,ESC）在人类遗传病学研究、疾病模型建立、器官再生以及动物物种改良和定向变异等方面的地位是其他类型的细胞不可取代的。但是,由于实验技术和体外培养条件的限制,除了小鼠、恒河猴和人之外,大鼠、猪、牛、羊等其他哺乳动物的ES细胞系被证明很难获得。先后有多个研究小组报道了他们利用新兴的诱导多能干细胞（induced pluripotent stem cells,iPS细胞）技术成功建立大鼠和猪的iPS细胞系的研究成果。迄今为止,这两个物种是在未成功建立ES细胞系之前利用iPS技术建立多能干细胞系的成功范例。这些研究对于那些还未建立ES细胞的物种建立多能干细胞系提供了一种新的方案,也将给这些物种的胚胎干细胞的建立、基因修饰动物的产生以及人类医疗事业的促进和发展带来新的希望。     

诱导多能干细胞向雄性生殖细胞分化诱导物的研究进展

诱导多能干细胞(induced pluripotent stem cells,iPSCs)是利用细胞重编程技术人工获得的与胚胎干细胞(embryonic stem cells,ESCs)功能类似的细胞,能分化成包括三胚层在内的所有细胞类型,并且规避了ESCs的伦理学争议和移植后的免疫排斥问题,具有十分广阔的应用前景。对iPSCs体外诱导为生殖细胞所用的诱导物及其诱导效果进行了综述,生殖细胞发育机制的研究有望促进未来生殖和发育技术的进步。     

成体干细胞多能性研究进展

成体干细胞是存在于机体组织的一类原始状态细胞,它们能够进行自我复制和特异分化,用于维持新陈代谢和创伤修复,年珲来越来越多的实验表明成体干细胞多向分化潜能,一种组织的干细胞可以分化成其他组织类型的细胞。作者介绍了国际上对成体干细胞概念的新看法,讨论了成体干细胞多能性的调控机理及与之相关的研究方法,还简要概括了成体干细胞在理论和临床应用上的重要意义。     

Dendritic cells derived from pluripotent stem cells: Potential of large scale production简

Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are promising sources for hematopoietic cells due to their unlimited growth capacity and the pluripotency. Dendritic cells (DCs), the unique immune cells in the hematopoietic system, can be loaded with tumor specific antigen and used as vaccine for cancer immunotherapy. While autologous DCs from peripheral blood are limited in cell number, hPSC-derived DCs provide a novel alternative cell source which has the potential for large scale production. This review summarizes recent advances in differentiating hPSCs to DCs through the intermediate stage of hematopoietic stem cells. Step-wise growth factor induction has been used to derive DCs from hPSCs either in suspension culture of embryoid bodies (EBs) or in co-culture with stromal cells. To fulfill the clinical potential of the DCs derived from hPSCs, the bioprocess needs to be scaled up to produce a large number of cells economically under tight quality control. This requires the development of novel bioreactor systems combining guided EB-based differentiation with engineered culture environment. Hence, recent progress in using bioreactors for hPSC lineage-specific differentiation is reviewed. In particular, the potential scale up strategies for the multistage DC differentiation and the effect of shear stress on hPSC differentiation in bioreactors are discussed in detail.     

Dendritic cells derived from pluripotent stem cells:Potential of large scale production

Human pluripotent stem cells(hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are promising sources for hematopoietic cells due to their unlimited growth capacity and the pluripotency. Dendritic cells(DCs), the unique immune cells in the hematopoietic system, can be loaded with tumor specific antigen and used as vaccine for cancer immunotherapy. While autologous DCs from peripheral blood are limited in cell number, hPSC-derived DCs provide a novel alternative cell source which has the potential for large scale production. This review summarizes recent advances in differentiating hPSCs to DCs through the intermediate stage of hematopoietic stem cells. Step-wise growth factor induction has been used to derive DCs from hPSCs either in suspension cultureof embryoid bodies(EBs) or in co-culture with stromal cells. To fulfill the clinical potential of the DCs derived from hPSCs, the bioprocess needs to be scaled up to produce a large number of cells economically under tight quality control. This requires the development of novel bioreactor systems combining guided EB-based differentiation with engineered culture environment. Hence, recent progress in using bioreactors for hPSC lineage-specific differentiation is reviewed. In particular, the potential scale up strategies for the multistage DC differentiation and the effect of shear stress on hPSC differentiation in bioreactors are discussed in detail.     

Pluripotent stem cell-derived neural stem cells: From basic research to applications

Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed.     

Neural differentiation from pluripotent stem cells:The role of natural and synthetic extracellular matrix

Neural cells differentiated from pluripotent stem cells(PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells(OPCs) and neural progenitor cells(NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices(ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of humanPSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.     

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix简

Neural cells differentiated from pluripotent stem cells (PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices (ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of human PSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.     

Microfluidic systems: A new toolbox for pluripotent stem cells

Conventional culture systems are often limited in their ability to regulate the growth and differentiation of pluripotent stem cells. Microfluidic systems can overcome some of these limitations by providing defined growth conditions with user-controlled spatiotemporal cues. Microfluidic systems allow researchers to modulate pluripotent stem cell renewal and differentiation through biochemical and mechanical stimulation, as well as through microscale patterning and organization of cells and extracellular materials. Essentially, microfluidic tools are reducing the gap between in vitro cell culture environments and the complex and dynamic features of the in vivo stem cell niche. These microfluidic culture systems can also be integrated with microanalytical tools to assess the health and molecular status of pluripotent stem cells. The ability to control biochemical and mechanical input to cells, as well as rapidly and efficiently analyze the biological output from cells, will further our understanding of stem cells and help translate them into clinical use. This review provides a comprehensive insignt into the implications of microfluidics on pluripotent stem cell research.     

Insight into generation of induced mesenchymal stem cells from induced pluripotent cells

Mesenchymal stem cells(MSCs)have the potential for use in cell-based regenerative therapies.Currently,hundreds of clinical trials are using MSCs for the treatment of various diseases.However,MSCs are low in number in adult tissues;they show heterogeneity depending upon the cell source and exhibit limited proliferative potential and early senescence in in vitro cultures.These factors negatively impact the regenerative potential of MSCs and therefore restrict their use for clinical applications.As a result,novel methods to generate induced MSCs(iMSCs)from induced pluripotent stem cells have been explored.The development and optimization of protocols for generation of iMSCs from induced pluripotent stem cells is necessary to evaluate their regenerative potential in vivo and in vitro.In addition,it is important to compare iMSCs with primary MSCs(isolated from adult tissues)in terms of their safety and efficacy.Careful investigation of the properties of iMSCs in vitro and their long term behavior in animals is important for their translation from bench to bedside.     

Application of mesenchymal stem cells derived from human pluripotent stem cells in regenerative medicine

Mesenchymal stem cells (MSCs) represent the most clinically used stem cells in regenerative medicine. However, due to the disadvantages with primary MSCs, such as limited cell proliferative capacity and rarity in the tissues leading to limited MSCs, gradual loss of differentiation during in vitro expansion reducing the efficacy of MSC application, and variation among donors increasing the uncertainty of MSC efficacy, the clinical application of MSCs has been greatly hampered. MSCs derived from human pluripotent stem cells (hPSC-MSCs) can circumvent these problems associated with primary MSCs. Due to the infinite self-renewal of hPSCs and their differentiation potential towards MSCs, hPSC-MSCs are emerging as an attractive alternative for regenerative medicine. This review summarizes the progress on derivation of MSCs from human pluripotent stem cells, disease modelling and drug screening using hPSC-MSCs, and various applications of hPSC-MSCs in regenerative medicine. In the end, the challenges and concerns with hPSC-MSC applications are also discussed.