Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 5 444
Page 15 of 545-
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.
-
Induction of inverted morphology in brain organoids by vertical-mixing bioreactors.
Organoid technology provides an opportunity to generate brain-like structures by recapitulating developmental steps in the manner of self-organization. Here we examined the vertical-mixing effect on brain organoid structures using bioreactors and established inverted brain organoids. The organoids generated by vertical mixing showed neurons that migrated from the outer periphery to the inner core of organoids, in contrast to orbital mixing. Computational analysis of flow dynamics clarified that, by comparison with orbital mixing, vertical mixing maintained the high turbulent energy around organoids, and continuously kept inter-organoid distances by dispersing and adding uniform rheological force on organoids. To uncover the mechanisms of the inverted structure, we investigated the direction of primary cilia, a cellular mechanosensor. Primary cilia of neural progenitors by vertical mixing were aligned in a multidirectional manner, and those by orbital mixing in a bidirectional manner. Single-cell RNA sequencing revealed that neurons of inverted brain organoids presented a GABAergic character of the ventral forebrain. These results suggest that controlling fluid dynamics by biomechanical engineering can direct stem cell differentiation of brain organoids, and that inverted brain organoids will be applicable for studying human brain development and disorders in the future.
-
Build-a-brain.
A major barrier in understanding nervous system development is modeling the cellular interactions that form the human brain. Recently, in the journal Nature, Lancaster et al. (2013) established a protocol for culturing pluripotent stem cell (PSC)-derived "cerebral organoids" that mimics the developing human brain's cellular organization, segregates into distinct brain regions, and models microcephaly.
-
Human iPSC-derived microglial cells protect neurons from neurodegeneration in long-term cultured adhesion brain organoids.
Brain organoid models have greatly facilitated our understanding of human brain development and disease. However, key brain cell types, such as microglia, are lacking in most brain organoid models. Because microglia have been shown to play important roles in brain development and pathologies, attempts have been made to add microglia to brain organoids through co-culture. However, only short-term microglia-organoid co-cultures can be established, and it remains challenging to have long-lasting survival of microglia in organoids to mimic long-term residency of microglia in the brain. In this study, we developed an adhesion brain organoid (ABO) platform that allows prolonged culture of brain organoids (greater than a year). Moreover, the long-term (LT)-ABO system contains abundant astrocytes and can support prolonged survival and ramification of microglia. Furthermore, we showed that microglia in the LT-ABO could protect neurons from neurodegeneration by increasing synaptic density and reducing p-Tau level and cell death in the LT-ABO. Therefore, the microglia-containing LT-ABO platform generated in this study provides a promising human cellular model for studying neuron-glia and glia-glia interactions in brain development and the pathogenesis of neurodegenerative diseases such as Alzheimer's disease.
-
Getting the right cells.
Fusing brain organoids with blood vessel organoids leads to the incorporation of non-neural endothelial cells and microglia into the brain organoids.
-
Translational Bioethical Decision-Making: Human Brain Organoids as a Case Study.
In an earlier essay, I advocated that translational bioethics uses the public's values, determined through social science, in its analysis of translational science technologies. It may be unclear what those values might be, and whether such a translational ethics would necessarily conclude that cutting edge technologies should not be developed. In this essay, I show the public's values relevant to human brain organoids and argue that a translational bioethics analysis using these values would support continued organoid research.
-
Controllable fusion of human brain organoids using acoustofluidics.
The fusion of human organoids holds promising potential in modeling physiological and pathological processes of tissue genesis and organogenesis. However, current fused organoid models face challenges of high heterogeneity and variable reproducibility, which may stem from the random fusion of heterogeneous organoids. Thus, we developed a simple and versatile acoustofluidic method to improve the standardization of fused organoid models via a controllable spatial arrangement of organoids. By regulating dynamic acoustic fields within a hexagonal acoustofluidic device, we can rotate, transport, and fuse one organoid with another in a contact-free, label-free, and minimal-impact manner. As a proof-of-concept to model the development of the human midbrain-to-forebrain mesocortical pathway, we acoustically fused human forebrain organoids (hFOs) and human midbrain organoids (hMOs) with the controllable alignment of neuroepithelial buds. We found that post-assembly, hMO can successfully project tyrosine hydroxylase neurons towards hFO, accompanied by an increase of firing rates and synchrony of excitatory neurons. Moreover, we found that our controllable fusion method can regulate neuron projection (e.g., range, length, and density), projection maturation (e.g., higher firing rate and synchrony), and neural progenitor cell (NPC) division in the assembloids via the initial spatial control. Thus, our acoustofluidic method may serve as a label-free, contact-free, and highly biocompatible tool to effectively assemble organoids and facilitate the standardization and robustness of organoid-based disease models and tissue engineering.
-
Generation of iPSC-Derived Brain Organoids for Drug Testing and Toxicological Evaluation.
The road to discover novel therapeutics for mental and neurological disorders has been severely hampered by the lack of access to relevant testing platforms. Currently, roughly 0.1% of drugs that show promise in preclinical testing make it to Phase I clinical trials, and 90% of those drugs go on to fail FDA approval. One of the reasons responsible for this low success rate is that conventional two-dimensional (2D) cell culture models are not accurate enough predictors of how drugs will work in humans. Three-dimensional (3D) brain organoids differentiated from induced pluripotent stem cells (iPSCs) to resemble specific parts of the human brain, which include architecture composition and physiology, can provide an alternative system that may lead to breakthroughs in key areas of drug testing and toxicological evaluation. Having reliable and scalable iPSC-derived brain organoid models that can much more accurately predict human drug responses will significantly increase success rate in developing treatments for brain-related disorders.
-
Vascularized human brain organoid on-chip.
Modelling the human brain in vitro has been extremely challenging due to the brain's intricate cellular composition and specific structural architecture. The recent emergence of brain organoids that recapitulate many key features of human brain development has thus piqued the interest of many to further develop and apply this in vitro model for various physiological and pathological investigations. Despite ongoing efforts, the existing brain organoids demonstrate several limitations, such as the lack of a functional human vasculature with perfusion capability. Microfluidics is suited to enhance such brain organoid models by enabling vascular perfusion and a curated blood-brain barrier microenvironment. In this review, we first provide an introduction to in vivo human brain development and present the state-of-the-art in vitro human brain models. We further elaborate on different strategies to improve the vascularized human brain organoid microenvironment using microfluidic devices, while discussing the current obstacles and future directions in this field.