皮肤类器官的构建、功能及其应用研究进展

皮肤类器官作为一种新型的类器官模型,不仅能高度模拟皮肤组织的生理结构和功能,更好地在不同体外环境下还原较真实的皮肤生态,还可以应用于皮肤发育研究、皮肤疾病病理研究及药物筛选等领域。在干细胞研究中,皮肤类器官模型可以在特殊的生境下对具有特定功能的皮肤细胞及其附属物进行重建和改造,以弥补现有体外皮肤模型在结构、功能等方面的不足。基于此,皮肤类器官将会在皮肤再生、组织修复、药物筛选及医学美容等方面扮演越来越重要的角色。本文详述了皮肤类器官构建中所参与的细胞来源及近年来的应用,并对未来皮肤类器官的发展与优化做出了展望。     

肝脏类器官的研究及应用进展

肝脏疾病易感性差异大且个体间的肝脏细胞存在明显的异质性,因此开发体外能够长期存活并具有代谢功能的人体类肝组织细胞模型,对治疗终末期肝病、开展肝脏致病机理研究及药物筛选具有重要意义。过去十年中,体外三维类器官模型发展迅猛,为疾病模拟、精准化治疗领域的研究提供了新的工具,显示出巨大潜力。肝脏类器官具有患者的基因表达与突变特征,在体外能够较长时间地保持肝脏细胞功能,已被应用于疾病模拟及药物有效性研究,并具有进行原位或异位移植发挥治疗作用的应用潜能。就干细胞、肝脏原代细胞等不同来源的肝脏类器官的发展及近年的研究进展作了综述,以期为肝脏类器官在疾病建模、药物发现和器官移植领域的研究和应用提供新的思路。     

心脏类器官

类器官是体外构建的一类由多种类型细胞组成的,与体内器官或组织高度相似的三维培养物,它能够模拟细胞所属器官的某些结构和生理功能。心血管疾病患病率及死亡率一直处于上升阶段,相关基础研究主要基于细胞和动物模型。心脏类器官是对传统心血管疾病模型的有效补充,在体外更真实和准确地反映人体心脏的生物学特性和功能,使其在疾病机制研究、药物开发、精准医疗和再生医学等领域具有广泛应用前景和独特优势。该文主要介绍了心脏类器官作为新一代疾病模型在心肌梗死、心力衰竭、遗传性心脏病和心律失常等方面的应用,并探讨了类器官技术未来的发展方向和面临的挑战。     

肠道类器官在肠疾病机制研究中的运用

肠道类器官由来自肠道的隐窝或干细胞在培养基质的三维（3D）支撑下构建形成,含有肠道的所有成熟细胞,已经成为研究肠道疾病机制全新且高效的平台。相较于二维（2D）细胞培养,肠道类器官不仅可以更加有效地模拟肠道的生理结构与功能,还可以在不同体外环境下更好地还原肠道的真实生态,因此在不同肠道疾病的发病机制研究中应用更为广泛。本文介绍了肠道类器官培养方式的新进展,综述了近年来肠道类器官在炎症性肠道疾病、结肠直肠癌和乳糜泻发病机制研究中的运用及进展,同时讨论了肠道类器官在药物研发与筛选方面的应用。     

骨类器官的构建及应用进展

骨骼疾病如骨质疏松、骨关节炎等已成为重要的人类健康问题,需要更深入地了解相关疾病的发病机制并开发更有效的治疗方法。由于2D细胞培养和动物实验等常规研究方法的局限性,近年来发展的类器官技术受到了极大关注。类器官作为干细胞衍生的自组织3D细胞簇,可以在体外更真实地模拟组织器官的复杂结构和生物功能。目前间充质干细胞、多能干细胞等衍生的骨类器官已逐步建立,不仅为疾病建模、药物筛选和生理病理基础研究提供了良好平台,还有望为骨缺损修复带来新希望。现对不同骨类器官模型的构建及主要应用进行概述,同时讨论了骨类器官培养面临的挑战,并对其未来发展进行展望,为构建结构功能更完善的骨类器官并将其应用于生物医学研究提供参考。     

类器官在发育与再生中的研究进展

类器官(organoid)作为体外模拟器官结构和功能的三维培养体系,已经广泛应用于发育研究、疾病建模和药物筛选。类器官在再生医学中具有重要的应用前景。胚胎干细胞、诱导多能性干细胞和多组织成体干/祖细胞来源的类器官再现了发育分化、稳态自我更新和组织损伤再生过程,为揭示发育和再生调控机制、明确生理病理进程提供了可能。近年来,多细胞类型的新型培养模式和单细胞测序等技术的应用促进了类器官的发展。该文总结了类器官在发育与再生中的最新研究成果,并就前沿技术在类器官研究中的应用进行了综述与展望。     

类器官的构建与应用进展

类器官是在体外经由干细胞驱动的, 形成具有来源器官显微解剖特征的多细胞三维结构且能自我更新的微组织。类器官能分化产生器官特异性的多种细胞类型,能重现对应器官的部分功能和空间架构,它的诞生为生命医学研究和临床应用注入了新动能,在癌症基础与临床研究、再生医学等领域表现出广阔的应用前景。对近些年国内外类器官研究进展进行综述,介绍其构建过程与培养体系,并详细阐述其作为体外研究模型的优缺点,为基于类器官的科学研究与应用提供了参考。     

类器官的构建与应用进展

类器官是在体外经由干细胞驱动的, 形成具有来源器官显微解剖特征的多细胞三维结构且能自我更新的微组织。类器官能分化产生器官特异性的多种细胞类型,能重现对应器官的部分功能和空间架构,它的诞生为生命医学研究和临床应用注入了新动能,在癌症基础与临床研究、再生医学等领域表现出广阔的应用前景。对近些年国内外类器官研究进展进行综述,介绍其构建过程与培养体系,并详细阐述其作为体外研究模型的优缺点,为基于类器官的科学研究与应用提供了参考。     

胰岛类器官研究进展

类器官是将具有多向分化潜能的干细胞或组织细胞在特定环境下培养分化成为能够模拟原生器官结构和功能的三维结构。类器官在各种疾病模型研究及药物筛选中发挥至关重要的作用。近年来,通过体外诱导胰腺组织或多能干细胞分化形成具有胰岛细胞功能的胰岛类器官研究成为热点,为胰岛相关疾病模型、药物研究以及糖尿病的治疗提供了新的手段。本文针对胰岛类器官的体外诱导方法及应用前景作一综述。     

类器官的研究进展及应用

随着人类生物学研究的不断深入,需建立新的模型系统为研究提供了有力的工具。虽然传统的研究模型已被广泛应用,但难以准确反映组织、器官在机体中的生理现象。类器官 (Organoid) 是来源于干细胞或器官祖细胞的三维细胞聚集体,可分化和自组织形成具有人体相应器官的部分特定功能和结构。由于类器官具有人源性,可模拟器官发育和形成,在体外长期扩增中具有基因组稳定性,并能够形成活体生物库进行高通量筛选等优势,成为近年来备受关注的体外模型。目前,利用类器官模型结合新兴的基因编辑、器官芯片、单细胞RNA测序技术等,能够突破传统模型的瓶颈,在器官水平上为疾病模型的建立、药物研发、精准医疗以及再生医学等提供有价值的信息。文中就类器官分类及特性、研究应用、与其他技术结合应用及展望这4个方面进行综述。     

Focus: Personalized Medicine: Value of Organoids from Comparative Epithelia Models

Organoids have tremendous therapeutic potential. They were recently defined as a collection of organ-specific cell types, which self-organize through cell-sorting, develop from stem cells, and perform an organ specific function. The ability to study organoid development and growth in culture and manipulate their genetic makeup makes them particularly suitable for studying development, disease, and drug efficacy. Organoids show great promise in personalized medicine. From a single patient biopsy, investigators can make hundreds of organoids with the genetic landscape of the patient of origin. This genetic similarity makes organoids an ideal system in which to test drug efficacy. While many investigators assume human organoids are the ultimate model system, we believe that the generation of epithelial organoids of comparative model organisms has great potential. Many key transport discoveries were made using marine organisms. In this paper, we describe how deriving organoids from the spiny dogfish shark, zebrafish, and killifish can contribute to the fields of comparative biology and disease modeling with future prospects for personalized medicine.     

Organoid model: A new hope for pancreatic cancer treatment?

Pancreatic cancer is a rapidly progressing disease with a poor prognosis. We still have many questions about the pathogenesis, early diagnosis and precise treatment of this disease. Organoids, a rapidly emerging technology, can simulate the characteristics of pancreatic tumors. Using the organoid model of pancreatic cancer, we can study and explore the characteristics of pancreatic cancer, thereby effectively guiding clinical practice and improving patient prognosis. This review introduces the development of organoids, comparisons of organoids with other preclinical models and the status of organoids in basic research and clinical applications for pancreatic cancer.     

The science and engineering of stem cell-derived organoids-examples from hepatic,biliary, and pancreatic tissues

The field of organoid engineering promises to revolutionize medicine with wide-ranging applications of scientific, engineering, and clinical interest, including precision and personalized medicine, gene editing, drug development, disease modelling, cellular therapy, and human development. Organoids are a three-dimensional (3D) miniature representation of a target organ, are initiated with stem/progenitor cells, and are extremely promising tools with which to model organ function. The biological basis for organoids is that they foster stem cell self-renewal, differentiation, and self-organization, recapitulating 3D tissue structure or function better than two-dimensional (2D) systems. In this review, we first discuss the importance of epithelial organs and the general properties of epithelial cells to provide a context and rationale for organoids of the liver, pancreas, and gall bladder. Next, we develop a general framework to understand self-organization, tissue hierarchy, and organoid cultivation. For each of these areas, we provide a historical context, and review a wide range of both biological and mathematical perspectives that enhance understanding of organoids. Next, we review existing techniques and progress in hepatobiliary and pancreatic organoid engineering. To do this, we review organoids from primary tissues, cell lines, and stem cells, and introduce engineering studies when applicable. We discuss non-invasive assessment of organoids, which can reveal the underlying biological mechanisms and enable improved assays for growth, metabolism, and function. Applications of organoids in cell therapy are also discussed. Taken together, we establish a broad scientific foundation for organoids and provide an in-depth review of hepatic, biliary and pancreatic organoids.     

Organogenesis in vitro

Organoids are three-dimensional structures that self-organize from human pluripotent stem cells or primary tissue, potentially serving as a traceable and manipulatable platform to facilitate our understanding of organogenesis. Despite the ongoing advancement in generating organoids of diverse systems, biological applications of in vitro generated organoids remain as a major challenge in part due to a substantial lack of intricate complexity. The studies of development and regeneration enumerate the essential roles of highly diversified nonepithelial populations such as mesenchyme and endothelium in directing fate specification, morphogenesis, and maturation. Furthermore, organoids with physiological and homeostatic functions require direct and indirect inter-organ crosstalk recapitulating what is seen in organogenesis. We herein review the evolving organoid technology at the cell, tissue, organ, and system level with a main emphasis on endoderm derivatives.     

Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between ani-mals and humans.Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs.Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids,including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs.The infected cells were ciliated,club,and alveolar type 2 (AT2) cells,which were sequentially located from the proximal to the distal airway and terminal alveoli,respectively.Addi-tionally,RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes,especially lipid metabolism,in addition to the well-known upregulation of immune response.Further,Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids.Therefore,human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.     

Circulating tumor cell-derived organoids: Current challenges and promises in medical research and precision medicine

Traditional 2D cell cultures do not accurately recapitulate tumor heterogeneity, and insufficient human cell lines are available. Patient-derived xenograft (PDX) models more closely mimic clinical tumor heterogeneity, but are not useful for high-throughput drug screening. Recently, patient-derived organoid cultures have emerged as a novel technique to fill this critical need. Organoids maintain tumor tissue heterogeneity and drug-resistance responses, and thus are useful for high-throughput drug screening. Among various biological tissues used to produce organoid cultures, circulating tumor cells (CTCs) are promising, due to relative ease of ascertainment. CTC-derived organoids could help to acquire relevant genetic and epigenetic information about tumors in real time, and screen and test promising drugs. This could reduce the need for tissue biopsies, which are painful and may be difficult depending on the tumor location. In this review, we have focused on advances in CTC isolation and organoid culture methods, and their potential applications in disease modeling and precision medicine.     

PRODUCTION OF ANOMALOUS STRUCTURES IN QUERCUS RUBRA L. CALLUS CULTURES

Internodal stem segments of 2–4-month-old Quercus rubra L. seedlings were cultured on Murashige and Skoog agar medium containing NAA and BA. Structures, termed organoids, were initiated from callus on medium containing 5 mg/1 NAA and 0.1 mg/1 BA. Organoids consisted of parenchymatous cells with a distinct epidermis and a continuous vascular system. Growth occurred principally by cell division throughout the parenchymatous tissue resulting in a variety of morphological shapes. Although no organized shoot meristems were observed, normal roots were produced; such roots were connected to the vascular system of the organoid.