Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 5 444
Страница 14 из 545-
Basic models to advanced systems: harnessing the power of organoids-based microphysiological models of the human brain.
Understanding the complexities of the human brain's function in health and disease is a formidable challenge in neuroscience. While traditional models like animals offer valuable insights, they often fall short in accurately mirroring human biology and drug responses. Moreover, recent legislation has underscored the need for more predictive models that more accurately represent human physiology. To address this requirement, human-derived cell cultures have emerged as a crucial alternative for biomedical research. However, traditional static cell culture models lack the dynamic tissue microenvironment that governs human tissue function. Advancedin vitrosystems, such as organoids and microphysiological systems (MPSs), bridge this gap by offering more accurate representations of human biology. Organoids, which are three-dimensional miniaturized organ-like structures derived from stem cells, exhibit physiological responses akin to native tissues, but lack essential tissue-specific components such as functional vascular structures and immune cells. Recent endeavors have focused on incorporating endothelial cells and immune cells into organoids to enhance vascularization, maturation, and disease modeling. MPS, including organ-on-chip technologies, integrate diverse cell types and vascularization under dynamic culture conditions, revolutionizing brain research by bridging the gap betweenin vitroandin vivomodels. In this review, we delve into the evolution of MPS, with a particular focus on highlighting the significance of vascularization in enhancing the viability, functionality, and disease modeling potential of organoids. By examining the interplay of vasculature and neuronal cells within organoids, we can uncover novel therapeutic targets and gain valuable insights into disease mechanisms, offering the promise of significant advancements in neuroscience and improved patient outcomes.
-
Microglia innately develop within cerebral organoids.
Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. The current consensus is that cerebral organoids consist of cells derived from the neuroectodermal lineage. This limits their value and applicability, as mesodermal-derived microglia are important players in neural development and disease. Remarkably, here we show that microglia can innately develop within a cerebral organoid model and display their characteristic ramified morphology. The transcriptome and response to inflammatory stimulation of these organoid-grown microglia closely mimic the transcriptome and response of adult microglia acutely isolated from post mortem human brain tissue. In addition, organoid-grown microglia mediate phagocytosis and synaptic material is detected inside them. In all, our study characterizes a microglia-containing organoid model that represents a valuable tool for studying the interplay between microglia, macroglia, and neurons in human brain development and disease.
-
Computing inspired by the brain: a journey from algorithms to organoids.
The human brain has long served as a blueprint for computation, guiding evolution from early symbolic systems to modern deep learning models. Despite these advances, traditional computing systems remain fundamentally limited in mirroring the remarkable flexibility, parallel processing and energy efficiency of the human brain. To address these limitations, neuromorphic computing was developed, which mimics the architecture and signaling behavior of biological neurons. Building on this foundation, a new frontier is now emerging-organoid intelligence (OI). OI uses lab-grown brain cellular structures, such as living neural organoids with electrical activity, synapse formation and primitive learning, as a substrate for computation. Here we trace the evolution of brain-inspired computing from symbolic logic systems to artificial neural networks, neuromorphic processors and finally biohybrid computers that incorporate living neural structures. We explore the transformative potential of OI along with the substantial technical, biological and ethical challenges it presents.
-
Message in a Scaffold: Natural Biomaterials for Three-Dimensional (3D) Bioprinting of Human Brain Organoids.
Brain organoids are invaluable tools for pathophysiological studies or drug screening, but there are still challenges to overcome in making them more reproducible and relevant. Recent advances in three-dimensional (3D) bioprinting of human neural organoids is an emerging approach that may overcome the limitations of self-organized organoids. It requires the development of optimal hydrogels, and a wealth of research has improved our knowledge about biomaterials both in terms of their intrinsic properties and their relevance on 3D culture of brain cells and tissue. Although biomaterials are rarely biologically neutral, few articles have reviewed their roles on neural cells. We here review the current knowledge on unmodified biomaterials amenable to support 3D bioprinting of neural organoids with a particular interest in their impact on cell homeostasis. Alginate is a particularly suitable bioink base for cell encapsulation. Gelatine is a valuable helper agent for 3D bioprinting due to its viscosity. Collagen, fibrin, hyaluronic acid and laminin provide biological support to adhesion, motility, differentiation or synaptogenesis and optimize the 3D culture of neural cells. Optimization of specialized hydrogels to direct differentiation of stem cells together with an increased resolution in phenotype analysis will further extend the spectrum of possible bioprinted brain disease models.
-
Generation of brain organoids from mouse ESCs via teratoma formation.
Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), can differentiate into all cell types in the body; therefore, they are used in the study of development and regenerative medicine. Neural lineage differentiation from PSCs is the initial step to study neurodevelopment and in vitro disease modeling. Brain organoids, which are composed of neural stem cells (NSCs) and differentiated neural lineage cell population, are a powerful in vitro system to mimic the brain tissue. Here, we aimed to establish a new method to generate brain organoids efficiently in a mouse model. We applied the in vivo teratoma formation method as a new approach to generate brain organoids. We induced teratoma formation using Sox1-GFP transgenic ESCs, in which green fluorescence protein (GFP) is expressed under the control of the early NSC marker Sox1. Sox1-GFP-expressing early NSCs were isolated as clumps and further cultured to generate brain organoids. Sox1-GFP ESC-derived brain organoids, composed of multiple layers of distinct cellular components (ventricle, ventricular zone, and cortical layer), were formed within 3 weeks of in vitro culture. We also found that neighboring cells (Sox1-GFP-) surrounding the Sox1-GFP+ clumps are essential for the formation of brain organoids. Thus, in vivo and in vitro conjugated systems-initial commitment in vivo and further specialization in vitro-could be one of the promising platforms for organoid formation that are universally applicable.
-
Differentiation of brain and retinal organoids from confluent cultures of pluripotent stem cells connected by nerve-like axonal projections of optic origin.
Advances in the study of neurological conditions have been possible because of pluripotent stem cell technologies and organoids. Studies have described the generation of neural ectoderm-derived retinal and brain structures from pluripotent stem cells. However, the field is still troubled by technical challenges, including high culture costs and variability. Here, we describe a simple and economical protocol that reproducibly gives rise to the neural retina and cortical brain regions from confluent cultures of stem cells. The spontaneously generated cortical organoids are transcriptionally comparable with organoids generated by other methods. Furthermore, these organoids showed spontaneous functional network activity and proteomic analysis confirmed organoids maturity. The generation of retinal and brain organoids in close proximity enabled their mutual isolation. Suspension culture of this complex organoid system demonstrated the formation of nerve-like structures connecting retinal and brain organoids, which might facilitate the investigation of neurological diseases of the eye and brain.
-
Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids.
Brain organoids have emerged as a novel model system for neural development, neurodegenerative diseases, and human-based drug screening. However, the heterogeneous nature and immature neuronal development of brain organoids generated from pluripotent stem cells pose challenges. Moreover, there are no previous reports of a three-dimensional (3D) hypoxic brain injury model generated from neural stem cells. Here, we generated self-organized 3D human neural organoids from adult dermal fibroblast-derived neural stem cells. Radial glial cells in these human neural organoids exhibited characteristics of the human cerebral cortex trend, including an inner (ventricular zone) and an outer layer (early and late cortical plate zones). These data suggest that neural organoids reflect the distinctive radial organization of the human cerebral cortex and allow for the study of neuronal proliferation and maturation. To utilize this 3D model, we subjected our neural organoids to hypoxic injury. We investigated neuronal damage and regeneration after hypoxic injury and reoxygenation. Interestingly, after hypoxic injury, reoxygenation restored neuronal cell proliferation but not neuronal maturation. This study suggests that human neural organoids generated from neural stem cells provide new opportunities for the development of drug screening platforms and personalized modeling of neurodegenerative diseases, including hypoxic brain injury.
-
CEP290 deficiency disrupts ciliary axonemal architecture in human iPSC-derived brain organoids.
Primary cilia are ubiquitous sensory organelles mediating various signaling modalities essential for development and cell homeostasis. Their dysfunction leads to ciliopathies, human disorders often affecting the central nervous system. CEP290 is a major ciliopathy-associated gene that encodes a centrosomal and ciliary transition zone protein. CEP290 has been implicated in different cellular functions, including cell cycle control, ciliogenesis and control of ciliary membrane protein content. To investigate CEP290 dysfunction in human neurons, we generated human induced pluripotent stem cell (iPSC)-derived brain organoids harboring CEP290 mutations. We found that CEP290 deficiency does not affect cell cycle progression or organoid formation, despite a tendency for less mature neuronal populations and formation of choroid plexus in mutant organoids. Expansion microscopy revealed morphologically abnormal ventricular cilia in the CEP290 mutant organoid cells with bulging ciliary membranes around splayed distal axonemal microtubules. Such ciliary abnormalities might represent a tissue-specific consequence revealed by studying a human neuronal organoid model.
-
Deciphering Complexity in Human Brain Organoids via a Novel Hurst Exponent Estimation.
Complexity is a hallmark of the human brain, emerging from the interaction of billions of neurons over time. Among various measures, the Hurst exponent (H) has been used to characterize temporal correlations in neuronal activity. Here, we introduce a method to estimate H directly from binary spike train series and propose that the coefficient of variation (CV) of H, rather than H itself, more accurately reflects neural complexity during organoid maturation. After validating the method on simulated data with embedded short- and long-range correlations, we applied it to cortical organoids derived from human-induced pluripotent stem cells, recorded via multielectrode arrays over 250 day. The analysis revealed a peak in complexity, as indicated by the CV of H, around the 100th day. At this stage, the organoids exhibited a wide repertoire of dynamic patterns, including both isolated spiking and highly synchronized network events. These results suggest that organoid activity undergoes a structured evolution in complexity and that CV of H provides a robust metric to capture this transition. Our approach offers a scalable tool for quantifying neural complexity in the developing brain.
-
Immunocompetent Brain Organoids with Microglia Allow Advanced Aging Research.
Aging is a complex and multifactorial process that significantly affects brain function and health, since it is commonly associated with the emergence of neurodegenerative diseases. Recent advances in stem cell technology have facilitated the development of brain organoids, three-dimensional structures that mimic key aspects of brain architecture and functionality. By incorporating microglia, the resident monocyte-derived immune cells of the central nervous system, immunocompetent brain organoids can provide a more physiologically relevant model for studying brain aging. This chapter explores the methodology of immunocompetent brain organoids for advanced aging research, detailing protocols for their generation from a co-culture of neural stem cells and primitive macrophage progenitors.