Spheroid

球体
  • 文章类型: Journal Article
    肿瘤学中的精准医学旨在根据患者肿瘤的基因组改变确定个体化治疗计划。它有助于为个体患者选择最有益的疗法。众所周知,没有病人的癌症是一样的,因此,不同的患者可能对常规治疗有不同的反应,精准医学,它取代了一刀切的方法,支持开发针对不同患者的特定癌症的定制治疗方法。作为3D细胞培养模型的患者特异性类器官或球体模型对于预测对抗癌药物的抗性以及在个性化医学中结合基因组分析来确定用于高通量药物筛选的最有效的癌症治疗是非常有希望的。因为肿瘤球体具有实体瘤的许多特征,反映了对药物和辐射的抗性,就像人类癌症一样,它们广泛用于药物筛选研究。根据分子谱分析的信息,用一些抗癌药物测试患者来源的3D癌症球体,可以揭示肿瘤细胞对药物的敏感性,并提供正确的化合物以有效对抗耐药细胞。鉴于许多患者对标准治疗没有反应,针对患者的治疗会更有效,毒性较小。与所有患者使用的标准方法相比,它们将更好地影响生存率。
    Precision medicine in oncology aims to identify an individualized treatment plan based on genomic alterations in a patient\'s tumor. It helps to select the most beneficial therapy for an individual patient. As it is now known that no patient\'s cancer is the same, and therefore, different patients may respond differently to conventional treatments, precision medicine, which replaces the one-size-fits-all approach, supports the development of tailored treatments for specific cancers of different patients. Patient-specific organoid or spheroid models as 3D cell culture models are very promising for predicting resistance to anti-cancer drugs and for identifying the most effective cancer therapy for high-throughput drug screening combined with genomic analysis in personalized medicine. Because tumor spheroids incorporate many features of solid tumors and reflect resistance to drugs and radiation, as in human cancers, they are widely used in drug screening studies. Testing patient-derived 3D cancer spheroids with some anticancer drugs based on information from molecular profiling can reveal the sensitivity of tumor cells to drugs and provide the right compounds to be effective against resistant cells. Given that many patients do not respond to standard treatments, patient-specific treatments will be more effective, less toxic. They will affect survival better compared to the standard approach used for all patients.
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  • 文章类型: Journal Article
    线粒体是负责维持细胞能量稳态的关键细胞器。因此,它们的功能障碍会对负责能量密集型代谢功能的细胞产生严重后果,如肝细胞。过去几十年的广泛研究已经确定线粒体功能受损是对乙酰氨基酚(APAP)过量诱导的肝损伤的病理生理学的中心特征。美国急性肝衰竭最常见的原因。虽然APAP过量后肝细胞线粒体氧化和硝化应激与线粒体通透性转变的诱导被很好地识别,最近的研究揭示了有关细胞器在APAP病理生理学中的作用的更多细节。这份简明扼要的回顾突出了这些新进展,确定了线粒体在APAP病理生理学中的核心作用,并将它们放在文献中早期信息的背景下。将讨论线粒体形态的适应性改变以及细胞铁在线粒体功能障碍中的作用以及APAP诱导的损伤后细胞器在肝脏恢复中的重要性。
    Mitochondria are critical organelles responsible for the maintenance of cellular energy homeostasis. Thus, their dysfunction can have severe consequences in cells responsible for energy-intensive metabolic function, such as hepatocytes. Extensive research over the last decades have identified compromised mitochondrial function as a central feature in the pathophysiology of liver injury induced by an acetaminophen (APAP) overdose, the most common cause of acute liver failure in the United States. While hepatocyte mitochondrial oxidative and nitrosative stress coupled with induction of the mitochondrial permeability transition are well recognized after an APAP overdose, recent studies have revealed additional details about the organelle\'s role in APAP pathophysiology. This concise review highlights these new advances, which establish the central role of the mitochondria in APAP pathophysiology, and places them in the context of earlier information in the literature. Adaptive alterations in mitochondrial morphology as well as the role of cellular iron in mitochondrial dysfunction and the organelle\'s importance in liver recovery after APAP-induced injury will be discussed.
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  • 文章类型: Journal Article
    Lately, 3D cell culture technique has gained a lot of appreciation as a research model. Augmented with technological advancements, the area of 3D cell culture is growing rapidly with a diverse array of scaffolds being tested. This is especially the case for spheroid cultures. The culture of cells as spheroids provides opportunities for unanticipated vision into biological phenomena with its application to drug discovery, metabolic profiling, stem cell research as well as tumor, and disease biology. Spheroid fabrication techniques are broadly categorised into matrix-dependent and matrix-independent techniques. While there is a profusion of spheroid fabrication substrates with substantial biological relevance, an economical, modular, and bio-compatible substrate for high throughput production of spheroids is lacking. In this review, we posit the prospects of elastin-like polypeptides (ELPs) as a broad-spectrum spheroid fabrication platform. Elastin-like polypeptides are nature inspired, size-tunable genetically engineered polymers with wide applicability in various arena of biological considerations, has been employed for spheroid culture with profound utility. The technology offers a cheap, high-throughput, reproducible alternative for spheroid culture with exquisite adaptability. Here, we will brief the applicability of 3D cultures as compared to 2D cultures with spheroids being the focal point of the review. Common approaches to spheroid fabrication are discussed with existential limitations. Finally, the versatility of elastin-like polypeptide inspired substrates for spheroid culture has been discussed.
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  • 文章类型: Systematic Review
    基于细胞的检测,在单层(2D)培养的细胞上进行,无疑是生物医学研究的宝贵工具。然而,由于在体内更好地模拟微环境和组织微结构的优点,三维(3D)细胞培养模型在过去几年中获得了相关性。最近的基于磁性的3D(m3D)细胞培养系统可用于此目的。这些系统基于通过悬浮将磁化细胞暴露在磁场中,生物打印,或环形成以促进细胞聚集成3D结构。然而,这些结构的成功发展取决于几个方法学特征,可以应用于模拟不同的人体组织。因此,使用Medline(通过Pubmed)进行系统评价,Scopus,和WebofScience(至2022年2月)数据库,以使用模仿人体组织的m3D培养物进行汇总研究。搜索生成了3784条记录,其中25人符合纳入标准。在这些研究中探索了这些m3D系统用于开发具有或不具有支架的同型或异型球体的可用性。我们还探讨了与磁性方法特别相关的方法差异。一般来说,m3D文化的发展一直在增加,生物打印和悬浮系统最常用于产生同型或异型培养物,主要是模仿人体组织的生理学,还要进行治疗性筛查。这篇系统的综述表明,在某些研究领域,这种方法的应用还很少被探索,比如癌症研究。
    Cell-based assays, conducted on monolayer (2D) cultured cells, are an unquestionably valuable tool for biomedical research. However, three-dimensional (3D) cell culture models have gained relevance over the last few years due to the advantages of better mimicking the microenvironment and tissue microarchitecture in vivo. Recent magnetic-based 3D (m3D) cell culture systems can be used for this purpose. These systems are based on exposing magnetized cells to magnetic fields by levitation, bioprinting, or ring formation to promote cell aggregation into 3D structures. However, the successful development of these structures is dependent on several methodological characteristics and can be applied to mimic different human tissues. Thus, a systematic review was performed using Medline (via Pubmed), Scopus, and Web of Science (until February 2022) databases to aggregate studies using m3D culture in which human tissues were mimicked. The search generated 3784 records, of which 25 met the inclusion criteria. The usability of these m3D systems for the development of homotypic or heterotypic spheroids with or without scaffolds was explored in these studies. We also explore methodological differences specifically related to the magnetic method. Generally, the development of m3D cultures has been increasing, with bioprinting and levitation systems being the most used to generate homotypic or heterotypic cultures, mainly to mimic the physiology of human tissues, but also to perform therapeutic screening. This systematic review showed that there are areas of research where the application of this method remains barely explored, such as cancer research.
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  • 文章类型: Journal Article
    目前,在微组织工程中,越来越需要在细胞和组织的培养中模拟体内微环境。凹陷的微孔变得越来越受欢迎,因为与传统的微孔相比,它们可以提供更接近体内环境的微环境。这可以促进细胞和组织的培养。这里,我们将总结凹面微孔的制作方法,以及它们在微组织工程中的应用。凹面微孔的制作方法包括传统方法,如光刻和蚀刻,光刻胶的热回流,激光烧蚀,精密计算机数控(CNC)铣削,和新兴技术,如表面张力法,软膜的变形,3D打印,微珠的成型,气泡,和冷冻的水滴。凹形微孔的制造正在从专业的微制造实验室转移到普通的生化实验室,以促进其应用并为用户提供便利。凹面微孔主要用于芯片上器官模型,包括3D细胞聚集体的形成和培养(球体,类器官,和胚胎)。研究人员还使用微孔来研究底物拓扑结构对细胞行为的影响。我们将简要回顾它们在微组织工程的不同方面的应用,并讨论凹微孔的进一步应用。我们认为,通过不同细胞系的3D细胞聚集体构建多器官芯片将是凹面微孔的流行应用,而将生理相关分子分析与3D培养平台整合将是不久的将来的另一个流行应用。此外,来自这些生物系统的3D细胞聚集体将在药物筛选和异种植入中找到更多应用。
    At present, there is an increasing need to mimic the in vivo micro-environment in the culture of cells and tissues in micro-tissue engineering. Concave microwells are becoming increasingly popular since they can provide a micro-environment that is closer to the in vivo environment compared to traditional microwells, which can facilitate the culture of cells and tissues. Here, we will summarize the fabrication methods of concave microwells, as well as their applications in micro-tissue engineering. The fabrication methods of concave microwells include traditional methods, such as lithography and etching, thermal reflow of photoresist, laser ablation, precision-computerized numerical control (CNC) milling, and emerging technologies, such as surface tension methods, the deformation of soft membranes, 3D printing, the molding of microbeads, air bubbles, and frozen droplets. The fabrication of concave microwells is transferring from professional microfabrication labs to common biochemical labs to facilitate their applications and provide convenience for users. Concave microwells have mostly been used in organ-on-a-chip models, including the formation and culture of 3D cell aggregates (spheroids, organoids, and embryoids). Researchers have also used microwells to study the influence of substrate topology on cellular behaviors. We will briefly review their applications in different aspects of micro-tissue engineering and discuss the further applications of concave microwells. We believe that building multiorgan-on-a-chip by 3D cell aggregates of different cell lines will be a popular application of concave microwells, while integrating physiologically relevant molecular analyses with the 3D culture platform will be another popular application in the near future. Furthermore, 3D cell aggregates from these biosystems will find more applications in drug screening and xenogeneic implantation.
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  • 文章类型: Journal Article
    Three-dimensional (3D) cell culture is often mentioned in the context of regenerative medicine, for example, for the replacement of ischemic myocardium with tissue-engineered muscle constructs. Additionally, 3D cell culture is used, although less commonly, in basic research, toxicology, and drug development. These applications have recently benefited from innovations in stem cell technologies allowing the mass-production of hiPSC-derived cardiomyocytes or other cardiovascular cells, and from new culturing methods including organ-on-chip and bioprinting technologies. On the analysis side, improved sensors, computer-assisted image analysis, and data collection techniques have lowered the bar for switching to 3D cell culture models. Nevertheless, 3D cell culture is not as widespread or standardized as traditional cell culture methods using monolayers of cells on flat surfaces. The many possibilities of 3D cell culture, but also its limitations, drawbacks and methodological pitfalls, are less well-known. This article reviews currently used cardiovascular 3D cell culture production methods and analysis techniques for the investigation of cardiotoxicity, in drug development and for disease modeling.
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    文章类型: Journal Article
    It is a commonly held belief that adult stem cells represent the \"seeds\" for normal cellular replenishment and also for carcinogenesis. The identification and characterization of stem cells for clinical therapeutic applications, however, is extremely challenging for a number of reasons. Recently, our group and others have attempted to isolate stem cells using spheroids from fresh surgical specimens and utilize them for in vitro and in vivo studies. This mini-review summarizes the major technical steps of these methods along with the primary findings. Besides, it critically analyzes the advantages and limitations of the concept and technical approaches. Finally, this mini-review presents our thoughts on the potential future directions of stem cell isolation and cancer stem cell-related research and clinical applications.
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