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Literatura académica sobre el tema "Neural organoids"

Autor: Grafiati

Publicado: 25 de mayo de 2024

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Artículos de revistas sobre el tema "Neural organoids"

Yu, Xiyao, Xiaoting Meng, Zhe Pei, et al. "Physiological Electric Field: A Potential Construction Regulator of Human Brain Organoids." International Journal of Molecular Sciences 23, no. 7 (2022): 3877. http://dx.doi.org/10.3390/ijms23073877.

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Brain organoids can reproduce the regional three-dimensional (3D) tissue structure of human brains, following the in vivo developmental trajectory at the cellular level; therefore, they are considered to present one of the best brain simulation model systems. By briefly summarizing the latest research concerning brain organoid construction methods, the basic principles, and challenges, this review intends to identify the potential role of the physiological electric field (EF) in the construction of brain organoids because of its important regulatory function in neurogenesis. EFs could initiate neural tissue formation, inducing the neuronal differentiation of NSCs, both of which capabilities make it an important element of the in vitro construction of brain organoids. More importantly, by adjusting the stimulation protocol and special/temporal distributions of EFs, neural organoids might be created following a predesigned 3D framework, particularly a specific neural network, because this promotes the orderly growth of neural processes, coordinate neuronal migration and maturation, and stimulate synapse and myelin sheath formation. Thus, the application of EF for constructing brain organoids in a3D matrix could be a promising future direction in neural tissue engineering.

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Pflug, Florian G., Simon Haendeler, Christopher Esk, Dominik Lindenhofer, Jürgen A. Knoblich, and Arndt von Haeseler. "Neutral competition explains the clonal composition of neural organoids." PLOS Computational Biology 20, no. 4 (2024): e1012054. http://dx.doi.org/10.1371/journal.pcbi.1012054.

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Neural organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progenies arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This high variability exceeds what can be explained by existing stochastic models of corticogenesis and indicates the existence of an additional source of stochasticity. To explain this variability, we introduce the SAN model which distinguishes Symmetrically diving, Asymmetrically dividing, and Non-proliferating cells. In the SAN model, the additional source of stochasticity is the survival time of a lineage’s pool of symmetrically dividing cells. These survival times result from neutral competition within the sub-population of all symmetrically dividing cells. We demonstrate that our model explains the experimentally observed variability of lineage sizes and derive the quantitative relationship between survival time and lineage size. We also show that our model implies the existence of a regulatory mechanism which keeps the size of the symmetrically dividing cell population constant. Our results provide quantitative insight into the clonal composition of neural organoids and how it arises. This is relevant for many applications of neural organoids, and similar processes may occur in other developing tissues both in vitro and in vivo.

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Logan, Sarah, Thiago Arzua, Yasheng Yan, et al. "Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles." Cells 9, no. 5 (2020): 1301. http://dx.doi.org/10.3390/cells9051301.

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Background: The development of 3D cerebral organoid technology using human-induced pluripotent stem cells (iPSCs) provides a promising platform to study how brain diseases are appropriately modeled and treated. So far, understanding of the characteristics of organoids is still in its infancy. The current study profiled, for the first time, the electrophysiological properties of organoids at molecular and cellular levels and dissected the potential age equivalency of 2-month-old organoids to human ones by a comparison of gene expression profiles among cerebral organoids, human fetal and adult brains. Results: Cerebral organoids exhibit heterogeneous gene and protein markers of various brain cells, such as neurons, astrocytes, and vascular cells (endothelial cells and smooth muscle cells) at 2 months, and increases in neural, glial, vascular, and channel-related gene expression over a 2-month differentiation course. Two-month organoids exhibited action potentials, multiple channel activities, and functional electrophysiological responses to the anesthetic agent propofol. A bioinformatics analysis of 20,723 gene expression profiles showed the similar distance of gene profiles in cerebral organoids to fetal and adult brain tissues. The subsequent Ingenuity Pathway Analysis (IPA) of select canonical pathways related to neural development, network formation, and electrophysiological signaling, revealed that only calcium signaling, cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling in neurons, glutamate receptor signaling, and synaptogenesis signaling were predicted to be downregulated in cerebral organoids relative to fetal samples. Nearly all cerebral organoid and fetal pathway phenotypes were predicted to be downregulated compared with adult tissue. Conclusions: This novel study highlights dynamic development, cellular heterogeneity and electrophysiological activity. In particular, for the first time, electrophysiological drug response recapitulates what occurs in vivo, and neural characteristics are predicted to be highly similar to the human brain, further supporting the promising application of the cerebral organoid system for the modeling of the human brain in health and disease. Additionally, the studies from these characterizations of cerebral organoids in multiple levels and the findings from gene comparisons between cerebral organoids and humans (fetuses and adults) help us better understand this cerebral organoid-based cutting-edge platform and its wide uses in modeling human brain in terms of health and disease, development, and testing drug efficacy and toxicity.

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Kim, Soo-hyun, and Mi-Yoon Chang. "Application of Human Brain Organoids—Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases." International Journal of Molecular Sciences 24, no. 15 (2023): 12528. http://dx.doi.org/10.3390/ijms241512528.

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Brain organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that reflect early brain organization. These organoids contain different cell types, including neurons and glia, similar to those found in the human brain. Human brain organoids provide unique opportunities to model features of human brain development that are not well-reflected in animal models. Compared with traditional cell cultures and animal models, brain organoids offer a more accurate representation of human brain development and function, rendering them suitable models for neurodevelopmental diseases. In particular, brain organoids derived from patients’ cells have enabled researchers to study diseases at different stages and gain a better understanding of disease mechanisms. Multi-brain regional assembloids allow for the investigation of interactions between distinct brain regions while achieving a higher level of consistency in molecular and functional characterization. Although organoids possess promising features, their usefulness is limited by several unresolved constraints, including cellular stress, hypoxia, necrosis, a lack of high-fidelity cell types, limited maturation, and circuit formation. In this review, we discuss studies to overcome the natural limitations of brain organoids, emphasizing the importance of combinations of all neural cell types, such as glia (astrocyte, oligodendrocytes, and microglia) and vascular cells. Additionally, considering the similarity of organoids to the developing brain, regionally patterned brain organoid-derived neural stem cells (NSCs) could serve as a scalable source for cell replacement therapy. We highlight the potential application of brain organoid-derived cells in disease cell therapy within this field.

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Mensah-Brown, Kobina G., James Lim, Dennis Jgamadze, et al. "96101 Temporal Evolution of Neural Activity in Human Brain Organoids." Journal of Clinical and Translational Science 5, s1 (2021): 23. http://dx.doi.org/10.1017/cts.2021.464.

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ABSTRACT IMPACT: This study will provide the essential characterization of intrinsic neural activity in human brain organoids, both at the single cell and network levels, to harness for translational purposes. OBJECTIVES/GOALS: Brain organoids are 3D, stem cell-derived neural tissues that recapitulate neurodevelopment. However, to levy their full translational potential, a deeper understanding of their intrinsic neural activity is essential. Here, we present our preliminary analysis of maturing neural activity in human forebrain organoids. METHODS/STUDY POPULATION: Forebrain organoids were generated from human iPSC lines derived from healthy volunteers. Linear microelectrode probes were employed to record spontaneous electrical activity from day 77, 100, and 130 organoids. Single unit recordings were collected during hour-long recordings, involving baseline recordings followed by glutamatergic blockade. Subsequently, tetrodotoxin, was used to abolish action potential firing. Single units were identified via spike sorting, and the spatiotemporal evolution of baseline neural properties and network dynamics was characterized. RESULTS/ANTICIPATED RESULTS: Nine organoids were recorded successfully (n=3 per timepoint). A significant difference in number of units was seen across age groups (F (2,6) = 6.4178, p = 0.0323). Post hoc comparisons by the Tukey HSD test showed significantly more units in day 130 (51.67 ±14.15) than day 77 (16.33 ±14.98) organoids. Mean firing rates were significantly different in organoids based on age, with drug condition also trending toward significance (F (6,12) = 9.97; p = 0.0028 and p = 0.08 respectively). Post hoc comparisons showed a higher baseline firing rate in day 130 (0.99Hz ±0.30) organoids than their day 77 counterparts at baseline (0.31Hz ±0.066) and glutamate blockade (0.31Hz ±0.045). Preliminary network analysis showed no modularity or small-world features; however, these features are expected to emerge as organoids mature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial analysis of brain organoid activity demonstrates changes in single unit properties as they mature. Additional work in this area, as well as further network analyses, will confer better sense of how to rationally utilize brain organoids for translational purposes.

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Birch, Jonathan. "When is a brain organoid a sentience candidate?" Molecular Psychology: Brain, Behavior, and Society 2 (October 18, 2023): 22. http://dx.doi.org/10.12688/molpsychol.17524.1.

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It would be unwise to dismiss the possibility of human brain organoids developing sentience. However, scepticism about this idea is appropriate when considering current organoids. It is a point of consensus that a brainstem-dead human is not sentient, and current organoids lack a functioning brainstem. There are nonetheless troubling early warning signs, suggesting organoid research may create forms of sentience in the near future. To err on the side of caution, researchers with very different views about the neural basis of sentience should unite behind the “brainstem rule”: if a neural organoid develops or innervates a functioning brainstem that registers and prioritizes its needs, regulates arousal, and leads to sleep-wake cycles, then it is a sentience candidate. If organoid research leads to the creation of sentience candidates, a moratorium or indefinite ban on the creation of the relevant type of organoid may be appropriate. A different way forward, more consistent with existing approaches to animal research, would be to require ethical review and harm-benefit analysis for all research on sentience candidates.

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Tanaka, Yoshiaki, and In-Hyun Park. "Regional specification and complementation with non-neuroectodermal cells in human brain organoids." Journal of Molecular Medicine 99, no. 4 (2021): 489–500. http://dx.doi.org/10.1007/s00109-021-02051-9.

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AbstractAlong with emergence of the organoids, their application in biomedical research has been currently one of the most fascinating themes. For the past few years, scientists have made significant contributions to deriving organoids representing the whole brain and specific brain regions. Coupled with somatic cell reprogramming and CRISPR/Cas9 editing, the organoid technologies were applied for disease modeling and drug screening. The methods to develop organoids further improved for rapid and efficient generation of cerebral organoids. Additionally, refining the methods to develop the regionally specified brain organoids enabled the investigation of development and interaction of the specific brain regions. Recent studies started resolving the issue in the lack of non-neuroectodermal cells in brain organoids, including vascular endothelial cells and microglia, which play fundamental roles in neurodevelopment and are involved in the pathophysiology of acute and chronic neural disorders. In this review, we highlight recent advances of neuronal organoid technologies, focusing on the region-specific brain organoids and complementation with endothelial cells and microglia, and discuss their potential applications to neuronal diseases.

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Katayama, Masafumi, Manabu Onuma, Noriko Kato, Nobuyoshi Nakajima, and Tomokazu Fukuda. "Organoids containing neural-like cells derived from chicken iPSCs respond to poly:IC through the RLR family." PLOS ONE 18, no. 5 (2023): e0285356. http://dx.doi.org/10.1371/journal.pone.0285356.

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There is still much room for development in pluripotent stem cell research on avian species compared to human stem cell studies. Neural cells are useful for the evaluation of risk assessment of infectious diseases since several avian species die of encephalitis derived from infectious diseases. In this study, we attempted to develop induced pluripotent stem cells (iPSCs) technology for avian species by forming organoids containing neural-like cells. In our previous study, we established two types iPSCs from chicken somatic cells, the first is iPSCs with PB-R6F reprogramming vector and the second is iPSCs with PB-TAD-7F reprogramming vector. In this study, we first compared the nature of these two cell types using RNA-seq analysis. The total gene expression of iPSCs with PB-TAD-7F was closer to that of chicken ESCs than that of iPSCs with PB-R6F; therefore, we used iPSCs with PB-TAD-7F to form organoids containing neural-like cells. We successfully established organoids containing neural-like cells from iPSCs using PB-TAD-7F. Furthermore, our organoids responded to poly:IC through the RIG-I-like receptor (RLR) family. In this study, we developed iPSCs technology for avian species via organoid formation. In the future, organoids containing neural-like cells from avian iPSCs can develop as a new evaluation tool for infectious disease risk in avian species, including endangered avian species.

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Zhou, Gang, Siyuan Pang, Yongning Li, and Jun Gao. "Progress in the generation of spinal cord organoids over the past decade and future perspectives." Neural Regeneration Research 19, no. 5 (2023): 1013–19. http://dx.doi.org/10.4103/1673-5374.385280.

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Abstract Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo. As emerging bioengineering methods have led to the optimization of cell culture protocols, spinal cord organoids technology has made remarkable advancements in the past decade. Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes. Moreover, fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment. These qualities make spinal cord organoids valuable tools for disease modeling, drug screening, and tissue regeneration. By utilizing this emergent technology, researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases. However, at present, spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine. Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

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Luo, Kevin. "Application of neural organoids in studying neurodegenerative diseases." Theoretical and Natural Science 15, no. 1 (2023): 166–70. http://dx.doi.org/10.54254/2753-8818/15/20240474.

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Neurodegenerative diseases are among the top causes of mortality and the aversion of DALYs (Disability-Adjusted Life Years) worldwide. Many attempts have been made to develop therapeutics to alleviate disease symptoms without much success. The preclinical models utilized in therapeutic testing are often inaccurate and cannot precisely translate into clinical studies. The introduction of neural organoids, a three-dimensional model grown from human-originated stem cells, was able to revolutionize the field of neurological drug development. Using induced pluripotent stem cell (iPSC), scientists are able to restore adult cells pluripotency and cultivate them into region specific brain organoids using a combination of growth factors, agonists, and inhibitors. These models have proven valuable in drug screen for myriad neurodegenerative disorders. To model such diseases, iPSCs are generated from patients with the respective diseases, and then cultivated in an environment that mimics the disease environment. For example, for Parkinsons disease, Wnt pathway inhibitors and the Sonic hedgehog agonist are used to induce midbrain neural progenitor cells from patients with risk factors. Despite neural organoids wide usage in screening for neurodegenerative disorders and drug testing, neural organoids present several limitations in their function, including a lack of complexity equivalent to that of the brain. This paper will discuss neural organoid technology and provide basic insight to its usage in drug screening and the field of neuroscience.

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Tesis sobre el tema "Neural organoids"

Omer, Attya. "Modeling human neural development and diseases using pluripotent stem cells." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS589.

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La microcéphalie est une maladie neurologique du nouveau-né qui se traduit par une circonférence réduite de la tête, une déficience intellectuelle et des défauts anatomiques du cerveau. La microcéphalie peut être la conséquence d’une infection, de stress environnementaux ou de mutations génétiques.Le cerveau commence à se former dès la cinquième semaine de grossesse et est majoritairement constitué de cellules souches neuronales, cellules qui conservent une capacité a se reproduire a l’identique sans se spécialiser. Cette première phase de prolifération est importante pour générer suffisamment de cellules. Suit une phase de différenciation, durant laquelle les cellules préalablement formées se différencient en deux groupes : les neurones, qui permettent de partager l’information grâce à des influx électriques, et les cellules gliales, qui soutiennent activement les fonctions des cellules neuronales.Je m’intéresse à un gène en particulier, KNL1, muté chez certains patients microcéphales. Grace aux nouvelles techniques d’édition du génome, j’ai reproduit la mutation retrouvée chez les patients dans des cellules souches pluripotentes humaines. En utilisant un modèle tridimensionnel (mini-cerveaux en culture), à partir de cellules souches neuronales, j’ai analysé de manière quantitative les étapes-clés de développement: les phases de prolifération et de différenciation.Mes travaux de recherche ont montré que les cellules souches neuronales portant la même mutation que les patients prolifèrent moins, réduisant le nombre de cellules initiales nécessaires au développement cérébral normal. Par ailleurs, les cellules souches neuronales se différencient prématurément en neurones et cellules gliales, ce qui réduit davantage le nombre le nombre final de cellules. Cette hypothèse a été confirmée par l’utilisation du modèle tridimensionnel, ou les mini-cerveaux sont plus petits que la normale.Cette étude est essentielle non seulement pour comprendre le développement de la maladie, mais également pour comprendre les étapes clés du développement du cerveau humain, et ne pourrait pas être mener à bien sur des modèles animaux. En outre, l’utilisation de cellules souches induites nous permet de ne pas utiliser de cellules embryonnaires, si nécessaire pour raisons d’éthique<br>Microcephaly is a neurological condition, resulting in patients having a small head circumference, intellectual impairment and brain anatomical defects. A pre-requisite for achieving a better understanding of the cellular events that contribute to the striking expansion of the human cerebral cortex is to elucidate cell-division mechanisms, which likely go awry in microcephaly. Most of the mutated genes identified in microcephaly patient encode centrosomal protein, KNL1 is the only gene that encodes a kinetochore protein, it plays a central role in kinetochore assembly and function during mitosis. While the involvement of centrosome functions is well established in the etiology of microcephaly, little is known about the contribution of KNL1.In an attempt to assess the role of KNL1 in brain development and its involvement in microcephaly, we generated isogenic human embryonic stem cell (hESC) lines bearing KNL1 patient mutations using CRISPR/Cas9-mediated gene targeting. We demonstrated that the point mutation leads to KNL1 reduction in neural progenitors. Moreover, mutant neural progenitors present aneuploidy, an increase in cell death and an abrogated spindle assembly checkpoint. Mutant fibroblasts, derived from hESC, do not have a reduced expression of KNL1 and do not present any defect in cell growth or karyotype, which highlight a brain-specific phenotype.The subsequent differentiation of mutant neural progenitors into two-dimensional neural culture leads to the depletion of neural progenitors in the favor of premature differentiation. We developed a three-dimensional neural spheroids model from neural progenitors and reported a reduced size of mutant neural spheroids, compare to control. Lastly, using knockdown and rescue assays, we proved that protein level of KNL1 is responsible of the premature differentiation and the reduced size.These data suggest that KNL1 has a brain-specific function during the development. Changes in its expression might contribute to the brain phenotypic divergence that appeared during human evolution

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Workman, Michael J. "Generating 3D human intestinal organoids with an enteric nervous system." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416570664.

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Klaus, Johannes [Verfasser], and Magdalena [Akademischer Betreuer] Götz. "Modeling neuronal heterotopias using iPSC derived neural stem cells, neurons and cerebral organoids derived from patients with mutations in FAT4 and DCHS1 / Johannes Klaus ; Betreuer: Magdalena Götz." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1148275789/34.

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Prudon, Nicolas. "Integrative study, from the cell to the animal model, of the development of a cell therapy for Parkinson's disease." Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0071.

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Un ensemble d'études précliniques soutient désormais le développement de thérapies de remplacement cellulaire dérivées de cellules souches pluripotentes pour soulager les symptômes moteurs chez les patients parkinsoniens. Le remplacement de la principale population cellulaire dysfonctionnelle au sein de la maladie, les neurones dopaminergiques A9, est l'objectif principal de ces thérapies. Pour y parvenir, la plupart des approches thérapeutiques impliquent la greffe de suspensions cellulaires de progéniteurs dopaminergiques. Cependant, une quantité considérable de cellules meurent pendant le processus de transplantation, les cellules étant confrontées à l'anoïkis. Une potentielle solution consiste à greffer des préparations solides, c'est-à-dire adopter un format cellulaire 3D. La cryopréservation de ce format reste un obstacle majeur et n'est pas exempte de causer des retards dans le délai avant l'apparition des effets, comme observé avec l'utilisation de suspensions unicellulaires de progéniteurs dopaminergiques cryopréservés. Le travail de cette thèse se concentre sur le développement de microtissus neuraux 3D en tant que thérapie cellulaire pour la maladie de Parkinson. L'utilisation d'une technologie d'encapsulation cellulaire à haut débit associée à des bioréacteurs pour fournir un environnement de culture 3D a permis la différenciation dirigée des hiPSC en microtissus neuraux. La différenciation correcte des microtissus neuraux vers une identité mésencéphalique a été confirmée à l'aide de méthodes orthogonales, en utilisant notamment la qRT-PCR, le RNAseq, la cytométrie en flux et la microscopie fluorescente. L'efficacité des microtissus neuraux a été démontrée de manière dose-dépendante dans des études précliniques, en utilisant le modèle de rat hémiparkinsonien lésé par la 6-OHDA. Les greffes ont été caractérisées par une analyse histologique post-mortem, démontrant la présence de neurones dopaminergiques humains projetant dans le striatum hôte. Le travail présenté ici est la première bioproduction d'une thérapie cellulaire pour la maladie de Parkinson dans un bioréacteur mis à échelle, conduisant à une récupération fonctionnelle complète des animaux 16 semaines après la transplantation d’un format cellulaire 3D cryopréservé<br>A breadth of preclinical studies is now supporting the rationale of pluripotent stem cell-derived cell replacement therapies to alleviate motor symptoms in Parkinsonian patients. Replacement of the primary dysfunctional cell population in the disease, i.e. the A9 dopaminergic neurons, is the major focus of these therapies. To achieve this, most therapeutical approaches involve grafting single-cell suspensions of DA progenitors. However, a considerable number of cells die during the transplantation process, as cells face anoïkis. One potential solution to address this challenge is to graft solid preparations, i.e. adopting a 3D format. Cryopreserving such format remains a major hurdle and is not exempt from causing delays in the time to effect, as observed with the use of cryopreserved single-cell DA progenitors. The work of this thesis focus on the development of 3D neural microtissues as a cell therapy for PD. The use of a high-throughput cell-encapsulation technology coupled with bioreactors to provide a 3D culture environment enabled the directed differentiation of hiPSCs into neural microtissues. The proper patterning of these neural microtissues into a midbrain identity was confirmed using orthogonal methods including qPCR, RNAseq, flow cytometry and immunofluorescent microscopy. The efficacy of the neural microtissues was demonstrated in a dose-dependent manner in non-clinical studies, using the 6-OHDA-lesioned hemiparkinsonian rat model. The grafts were characterized by post-mortem histological analysis, demonstrating the presence of human dopaminergic neurons projecting into the host striatum. The work reported here is the first bioproduction of a cell therapy for Parkinson’s disease in a scalable bioreactor, leading to a full behavioural recovery 16 weeks in the animal model after transplantation using cryopreserved 3D cell format

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FARIA, PEREIRA MARLENE CRISTINA. "EPIGENETIC AND FUNCTIONAL ASSESSMENT OF ENHANCEROPATHIES ACROSS HUMAN MODELS: FOCUS ON GABRIELE-DE VRIES SYNDROME." Doctoral thesis, Università degli Studi di Milano, 2022. https://hdl.handle.net/2434/945230.

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Yin Yang 1 (YY1) is a ubiquitous zinc finger transcription factor (TF) that occupies active enhancers and promoters contributing to physical interactions between these regions via DNA looping. Increasing evidence shows that disruption of non-coding regions such as enhancers is prevalent across different neurodevelopmental disorders (NDDs) with intellectual disability (ID) features. Indeed, YY1 haploinsufficiency causes a NDD with ID, named Gabriele-de Vries syndrome (GADEVS). Although it is known that YY1 controls the expression of a dazzling list of genes and influences various cellular processes in numerous cell types, the impact of this TF in the neurodevelopment of the human cortex is yet to be unraveled. By taking advantage of disease-modeling as a tool to investigate the pathogenesis of GADEVS across different time points and tissues we gathered new insights about how YY1 haploinsufficiency exerts such a dramatic phenotype in individuals carrying mutations. We reprogrammed patient-derived and healthy somatic cells into induced-pluripotent stem cells (iPSCs) and observed, already at the pluripotent stage, a major transcriptional dysregulation. Moreover, since YY1-mutated patients exhibit ID features, we differentiated our cohort of iPSCs into cortical neurons as well organoids and were able to capture stage-specific striking features, not only at the transcriptomic level, but also structural and compartmentalization impairments. Of note, YY1-mutated neurons displayed synaptic disparities, sufficient to induce astrogliosis-like features in surrounding astrocytes, both shown to be critical for proper brain function and plasticity forms in the CNS. Instead, in cortical organoids we recapitulated features of abnormal ventricle formation, pathological hallmarks observed in GADEVS patients and mice models followed by ID and developmental delay. This study showed, for the first time, the molecular signatures that possibly lead to cognitive defects in human patients and provide the first solid foundation for the development of therapeutic strategies and drug screening in the future.

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Baillie-Johnson, Peter. "The generation of a candidate axial precursor in three dimensional aggregates of mouse embryonic stem cells." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267818.

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Textbook accounts of vertebrate embryonic development have been based largely upon experiments on amphibian embryos, which have shown that the tissues of the trunk and tail are organised from distinct precursors that existed during gastrulation. In the mouse and chick, however, retrospective clonal analyses and transplantation experiments have demonstrated that the amniote body instead arises progressively from a population of axial precursors that are common to both the neural and mesodermal tissues of the trunk and tail. For this reason, they are known as neuro-mesodermal progenitors (NMps). Detailed studies of NMps have been precluded by their lack of a unique gene expression profile and the technical difficulties associated with isolating them from the embryo. Mouse embryonic stem cells (ESCs) provide the possibility of instead deriving them in vitro. ESCs have been used to model developmental processes, partly through large cellular aggregates known as embryoid bodies. These structures do not, however, resemble the axial organisation of the embryo and they develop in a disordered manner. This thesis presents a novel culture system of small, three-dimensional aggregates of ESCs (gastruloids) that can recreate the events of early post-implantation development, including axial elongation. Gastruloids are the first ESC-based model for axial elongation morphogenesis; this body of work characterises their development and identifies a candidate population of NMps within their elongating tissues. Additionally, this work establishes a xenotransplantation assay for testing the functional properties of in vitro-derived NMp populations in the chicken embryo and applies it to NMps from gastruloid cultures. The results of this assay show that gastruloids are a credible source of NMps in vitro and therefore offer a new experimental means to interrogate their properties. The use of gastruloids to recreate embryonic development has implications for basic research as a synthetic system and for the therapeutic derivation of other embryonic progenitors through bioengineering.

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Eldred, Megan. "Investigating cellular and molecular mechanisms of neuronal layering in self-organising aggregates of zebrafish retinal cells." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284080.

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The central nervous system is a complex, yet well-organised, often laminated, tissue. This robust organisation is evident in the architecture of the retina: consisting of 5 different neuronal types organised into distinct layers: Retinal Ganglion Cell (RGC), Amacrine Cell (AC), Bipolar Cell (BP), Horizontal Cell (HC) and Photoreceptor cell (PR) layers. This remarkable organisation is evolutionarily conserved in vertebrates, yet little is known about the mechanisms by which these cells form the correct layers. Live imaging has revealed overlapping periods of birth and extensive inter-digitation followed by cells sorting out into their appropriate positions, suggesting cell-cell interactions are important. To investigate possible cellular and molecular mechanisms responsible for the establishment of the tissue architecture I developed an organoid culture system for zebrafish retinal cells. To identify the cells in culture I used a Spectrum of Fates fish line which is a multiply transgenic line in which each retinal cell type can be identified based on expression of a combination of fluorescently tagged cell fate markers. The development of the protocol by which I cultured the cells and observed their cell-cell interactions involved establishing the best methods to dissociate and culture zebrafish retinal cells in a non-adhesive environment, then imaging the resulting reaggregates to examine the position of the different retinal cell types. By doing this I observed their inherent self-organising properties, in the absence of extrinsic cues or scaffolds. These cells appeared to be arranged in an inside-out layering, although all cell types are layered in the same relative order as they are in vivo. To analyse the organization in these aggregates I developed a Matlab script in collaboration with Leila Muresan which analyses the relative positioning of cells in concentric rings from the periphery to the centre of the aggregates according to the cell fate-tagged fluorescent markers. The script then fits this data as an empirical cumulative distribution function for different groups of cells to determine how spatially distinct populations of cells are. This gave me my measure of organisation. I then investigated the cell-cell interactions involved in this self-organisation by genetically or pharmacologically removing individual cell types and assaying the resulting organisation of the reaggregated, cell-type deficient, retinal organoids. I revealed that Müller Glia are important for retinal cell self-organisation. I also investigated the role of Retinal Pigment Epithelial (RPE) cells and Retinal Ganglion Cells and found they had no impact on the ability of the remaining cell types to organize. I began to investigate the role of Amacrine Cells but found that retinas void of ACs were susceptible to disaggregating in our dissection setup, preventing me from collecting the material needed for culture. I also investigated the role of candidate molecules in this system and revealed that R-Cognin is critical for retinal cells to reaggregate. Not only can I remove cells or molecules from the system, but I show how it can also be manipulated to replace molecules of interest such as laminin, by coating beads with the substance of choice and placing it amongst the cells to see if their organisational behaviour is affected. In summary, I have developed a system which provides a simple and easy platform to manipulate in various ways to help us potentially reveal some of the important players in neuronal patterning.

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Forlivesi, Claudio. "Biomateriali e 3D bioprinting nella rigenerazione neurale." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/17888/.

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Il sistema nervoso centrale svolge un ruolo chiave nella raccolta, integrazione ed elaborazione delle informazioni provenienti dagli organi di senso e dall’ambiente interno dell’organismo. La sua struttura, formata da una complessa rete neurale finemente organizzata può essere soggetta a danni di vario tipo, che ne minano le funzionalità. Per far fronte a tale evenienza, negli ultimi anni, sta emergendo una nuova scienza dal carattere fortemente multidisciplinare, ovvero la medicina neurorigenerativa. Essa comprende l’ingegneria tissutale, che mira all’ingegnerizzazione dei materiali per la produzione di supporti per la rigenerazione (scaffold), la neurologia, e l’ingegneria biomedica. Scopo di questa tesi è stato quello di passare in rassegna le ricerche più recenti sui materiali impiegati per la medicina neurorigenerativa, così come le tecniche e le tecnologie emergenti per il loro processo. In particolare, i polimeri naturali e di sintesi rappresentano una reale potenzialità per possibili interventi terapeutici. D’altra parte, tecnologie di processo quali l’electrospinning e la stampa tridimensionale (3D BIOPRINTING) hanno consentito di progredire notevolmente nella fabbricazione di supporti finalizzati allo sviluppo di impianti neurorigenerativi eterologhi o coadiuvanti l’impianto autologo. In particolare, il 3D Bioprinting è una tecnologia che ha la potenzialità di consentire, in un prossimo futuro, di riprodurre con precisione sempre maggiore la delicata organizzazione spaziale e strutturale gerarchica della matrice extracellulare neuronale. I vantaggi e le applicazioni del Bioprinting sono potenzialmente vastissimi e ancora in fase di esplorazione. L’impatto di nuove tecnologie, nuovi materiali e tecniche bioigegneristiche d’avanguardia potrebbero rappresentare non solo un passo avanti nel campo della rigenerazione neurale, ma anche per la comprensione di processi fisiologici ed ancor di più patofisiologici del Sistema Nervoso Centrale.

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Pagliaro, Sarah Beatriz De Oliveira. "Transcriptional control induced by bcr-abl and its role in leukemic stem cell heterogeneity. Single-Cell Transcriptome in Chronic Myeloid Leukemia: Pseudotime Analysis Reveals Evidence of Embryonic and Transitional Stem Cell States Single Cell Transcriptome in Chronic Myeloid Leukemia (CML): Pseudotime Analysis Reveals a Rare Population with Embryonic Stem Cell Features and Druggable Intricated Transitional Stem Cell States A novel neuronal organoid model mimicking glioblastoma (GBM) features from induced pluripotent stem cells (iPSC) Experimental and integrative analyses identify an ETS1 network downstream of BCR-ABL in chronic myeloid leukemia (CML)." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ032.

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La leucémie myéloïde chronique est une hématopoïèse maligne clonale, caractérisée par l'acquisition de la translocation t (9;22) conduisant au chromosome Ph1 et à son homologue l'oncogène BCR-ABL, dans une cellule souche hématopoïétique très primitive. La LMC est un modèle de thérapies ciblées, car il a été démontré que la preuve de la faisabilité du ciblage de l'activité tyrosine kinase (TK) BCR-ABL à l'aide d'inhibiteurs de TK (TKI) entraîne des réponses et des rémissions majeures. Cependant, les problèmes actuels rencontrés dans ces thérapies sont la résistance des cellules souches leucémiques primitives et leur persistance qui serait liée à l'hétérogénéité des cellules souches au moment du diagnostic, ce qui conduit à la sélection clonale de cellules résistant aux thérapies TKI. J'ai appliqué la technologie de l'analyse du transcriptome des cellule uniques aux cellules de la LMC en utilisant un panel de gènes impliqués dans différentes voies, combinée à l'analyse d'inférence de trajectoire au modèle d'expression des gènes. Les résultats ont montré un état transitoire des cellules souches comprenant des gènes embryonnaires identifiés dans les cellules de la LMC au moment du diagnostic, ce qui pourrait contribuer à la résistance et à la persistance de la LSC. En outre, l'oncoprotéine Bcr-Abl est la tyrosine kinase constitutivement active produite par le gène chimérique BCR-ABL dans la leucémie myéloïde chronique (LMC). Les cibles transcriptionnelles de Bcr-Abl dans les cellules leucémiques n'ont pas été étudiées de manière approfondie. Une expérience de transcriptome utilisant la lignée cellulaire UT7 hématopoïétique exprimant BCR-ABL, a identifié la surexpression du facteur d'élongation eucaryote kinase 2 (eEF2K) qui joue un rôle majeur dans la survie des cellules en cas de privation de nutriments. Dans l'ensemble, les données suggèrent que la surexpression de eEF2K dans la LMC est associée à une sensibilité accrue à la privation de nutriments<br>Chronic myeloid leukemia is a clonal hematopoietic malignancy, characterized by the acquisition of the t (9;22) translocation leading to Ph1 chromosome and its counterpart BCR-ABL oncogene, in a very primitive hematopoietic stem cell. CML is a model of targeted therapies as the proof of concept of the feasibility of targeting the tyrosine kinase (TK) activity BCR-ABL using TK inhibitors (TKI) has been shown to lead to major responses and remissions. However, the current problems encountered in these therapies are primitive leukemic stem cells resistance and their persistence which is thought to be related to the heterogeneity of the stem cells at diagnosis leading to clonal selection of cells resisting to TKI therapies. I have applied the technology of single cell transcriptome analysis to CML cells using a panel of genes involved in different pathways combined with trajectory inference analysis to the gene expression pattern. The results showed a transitional stem cell states including embryonic genes identified in CML cells at diagnosis which could contribute to LSC resistance and persistence. Furthermore, the oncoprotein Bcr-Abl is the constitutively active tyrosine kinase produced by the chimeric BCR-ABL gene in chronic myeloid leukemia (CML). The transcriptional targets of Bcr-Abl in leukemic cells have not been extensively studied. A transcriptome experiment using the hematopoietic UT7 cell line expressing BCR-ABL, has identified the overexpression of eukaryotic elongation factor kinase 2 (eEF2K) which plays a major role in the survival of cells upon nutrient deprivation. Overall, the data suggest that overexpression of eEF2K in CML is associated with an increased sensitivity to nutrient-deprivation

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Libros sobre el tema "Neural organoids"

The Emerging Field of Human Neural Organoids, Transplants, and Chimeras. National Academies Press, 2021. http://dx.doi.org/10.17226/26078.

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National Academies of Sciences, Engineering, and Medicine. Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance. National Academies Press, 2021.

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Affairs, Policy and Global, Technology, and Law Committee on Science, National Academies of Sciences, Engineering, and Medicine, and Committee on Ethical, Legal, and Regulatory Issues Associated with Neural Chimeras and Organoids. Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance. National Academies Press, 2021.

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Affairs, Policy and Global, Technology, and Law Committee on Science, National Academies of Sciences, Engineering, and Medicine, and Committee on Ethical, Legal, and Regulatory Issues Associated with Neural Chimeras and Organoids. The Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance. National Academies Press, 2022.

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Capítulos de libros sobre el tema "Neural organoids"

Sakaguchi, Hideya, and Nozomu Takata. "Stem Cell-Derived Neural Organoids: From the Origin to Next Generation." In Handbook of Stem Cell Applications. Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-99-0846-2_6-1.

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Sebastian, Rebecca, Narciso S. Pavon, Yoonjae Song, Karmen T. Diep, and ChangHui Pak. "Method to Generate Dorsal Forebrain Brain Organoids from Human Pluripotent Stem Cells." In Stem Cell-Based Neural Model Systems for Brain Disorders. Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3287-1_13.

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Murray, Liam, Meagan N. Olson, Nathaniel Barton, Pepper Dawes, Yingleong Chan, and Elaine T. Lim. "FACS-Based Sequencing Approach to Evaluate Cell Type to Genotype Associations Using Cerebral Organoids." In Stem Cell-Based Neural Model Systems for Brain Disorders. Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3287-1_15.

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Takahashi, Toshio. "New Trends and Perspectives in the Function of Non-neuronal Acetylcholine in Crypt–Villus Organoids in Mice." In Methods in Molecular Biology. Springer New York, 2016. http://dx.doi.org/10.1007/7651_2016_1.

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Gong, Jing, Jiahui Kang, Minghui Li, Xiao Liu, Jun Yang, and Haiwei Xu. "Applications of Neural Organoids in Neurodevelopment and Regenerative Medicine." In Organoids [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.104044.

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Recent advances in stem cell technologies have enabled the application of three-dimensional neural organoids for exploring the mechanisms of neurodevelopment and regenerative medicine. Over the past decade, series of studies have been carried out to investigate the cellular and molecular events of human neurogenesis using animal models, while the species differences between animal models and human being prevent a full understanding of human neurogenesis. Human neural organoids provide a new model system for gaining a more complete understanding of human neural development and their applications in regenerative medicine. In this chapter, the recent advances of the neural organoids of the brain and retina as well as their applications in neurodevelopment and regenerative medicine are reviewed.

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Bordoni, Matteo, Valentina Fantini, Orietta Pansarasa, and Cristina Cereda. "From Neuronal Differentiation of iPSCs to 3D Neural Organoids: Modeling of Neurodegenerative Diseases." In Recent Advances in Neurodegeneration. IntechOpen, 2019. http://dx.doi.org/10.5772/intechopen.80055.

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Evans, John H. "Consciousness, the Human-Animal Foundational Distinction, and Ephemeral Connections to Humans." In Disembodied Brains. Oxford University PressNew York, 2024. http://dx.doi.org/10.1093/oso/9780197750704.003.0004.

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Abstract This chapter provides the results of the analysis of the public’s views. While bioethicists and scientists are primarily concerned that an organoid or a neuro-chimera could acquire increased consciousness, the public does not appear to be greatly concerned with consciousness. Rather, evidence shows that the public is principally concerned about violating the foundational distinction between humans and animals. In its strongest form, this concern produces not only opposition to chimeras but a disgust-driven backlash against them, with the public suggesting that they be treated worse than others of their species. This chapter also shows that the public does indeed believe in ephemeral connections to disembodied human parts like organoids, and that such belief is associated with opposition to creating organoids.

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Tang, Chunling, Xinghui Wang, Eileen Gentleman, and Nicholas A. Kurniawan. "Production of Neuroepithelial Organoids from Human-Induced Pluripotent Stem Cells for Mimicking Early Neural Tube Development." In Methods in Molecular Biology. Springer US, 2024. http://dx.doi.org/10.1007/7651_2024_546.

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Jacob, Fadi, Jordan G. Schnoll, Hongjun Song, and Guo-li Ming. "Building the brain from scratch: Engineering region-specific brain organoids from human stem cells to study neural development and disease." In Current Topics in Developmental Biology. Elsevier, 2021. http://dx.doi.org/10.1016/bs.ctdb.2020.12.011.

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Sharma, Maryada, Sonal Jangra, Shalini Dhiman, et al. "Leveraging neural crest pluripotency to extend retinal and craniofacial niches for building neurovascular organoids—a theranostic and drug development perspective." In The Eye, Volume 4. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-323-99987-8.00007-2.

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Actas de conferencias sobre el tema "Neural organoids"

Shettigar, Nandan, Lamees El Nihum, Ashok Thyagarajan, Debjyoti Banerjee, and Robert Krencik. "Design, Microfabrication and Testing of Brain-on-a-Chip (BOC) Platform Using Neural Organoids (Spheroids)." In ASME 2021 Fluids Engineering Division Summer Meeting. American Society of Mechanical Engineers, 2021. http://dx.doi.org/10.1115/fedsm2021-65894.

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Abstract Three-dimensional (3D) organoid engineering aims to steer cell aggregates toward physiological mimicking of human tissue and organ systems at the cellular level, essentially serving as tissue and organ proxies that recapitulate biological parameters (e.g., spatial organization of heterogenous tissue-specific cells, cell-cell interactions, etc.). Currently, attempts at generation of brain organoids do not mature beyond the prenatal brain equivalent, the major obstacle being the lack of vascularization in the initial embryoid bodies that ultimately limit the growth and maturation of the organoids. Thus, attention is turned toward generation of a brain-on-a-chip model that can serve as a relevant model of the human brain in its recapitulation of the neuronal circuit (i.e., organoid-on-chip or “OOC”; brain-on-chip or “BOC”). In this study, soft lithography techniques using polydimethylsiloxane (PDMS) elastomers were implemented to fabricate a microfluidic chip to serve as a BOC/OOC. A mold was fabricated using 3D printing for performing soft lithography of the BOC (followed by bonding on to a glass slide). Neural organoids (spheroids) were dispensed into the BOC using a pipette. The BOC was designed for the organoids to be captured at specific locations using micro-pillars that are located strategically within the microchannel network. Copper microelectrodes were manually inserted into the device through specially designed ports to serve as probes (as electrical sensors) and were mounted strategically for detection of electrical response from the organoids. Experiments were conducted to acquire and analyze the electrical response of the organoids when subjected to a variety of conditions (and stimuli). Two sets of organoids were tested in these experiments: organoids that are light responsive (LR) and organoids that are not light responsive (NLR). The set of experiments performed in this study include: control experiments using pure media (exposed to light), control experiments performed using media decanted from organoid suspensions (with and without exposure to light for both LR and NLR), baseline tests using organoids not exposed to light (control experiments for both LR and NLR), and experiments involving organoids exposed to variety of stimuli (light exposure, saline solution, etc. for both LR and NLR).

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Wilson, Madison, Martin Thunemann, Francesca Puppo, et al. "Transparent neural interface for in vivo interrogation of human organoids." In Neural Imaging and Sensing 2021, edited by Qingming Luo, Jun Ding, and Ling Fu. SPIE, 2021. http://dx.doi.org/10.1117/12.2579350.

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MacDonald, Michael, Randy Fennel, Asha Singanamalli, et al. "Improved automated segmentation of human kidney organoids using deep convolutional neural networks." In Image Processing, edited by Bennett A. Landman and Ivana Išgum. SPIE, 2020. http://dx.doi.org/10.1117/12.2549830.

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Wilson, Madison N., Martin Thunemann, Francesca Puppo, et al. "Investigation of functional integration of cortical organoids transplanted in vivo towards future neural prosthetics applications." In 2023 11th International IEEE/EMBS Conference on Neural Engineering (NER). IEEE, 2023. http://dx.doi.org/10.1109/ner52421.2023.10123847.

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Zhang, Jinqiu, Jolene Ooi, Sarah R. Langley, et al. "A48 Expanded HTT cag repeats disrupt the balance between neural progenitor expansion and differentiation in isogenic human cerebral organoids." In EHDN 2018 Plenary Meeting, Vienna, Austria, Programme and Abstracts. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/jnnp-2018-ehdn.46.

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Pitta, Marina Galdino da Rocha, Jordy Silva de Carvalho, Luzilene Pereira de Lima, and Ivan da Rocha Pitta. "iPSC therapies applied to rehabilitation in parkinson’s disease." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.022.

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Background: Parkinson’s disease (PD) is a neurological disorder that affects movement, mainly due to damage and degeneration of the nigrostriatal dopaminergic pathway. The diagnosis is made through a clinical neurological analysis where motor characteristics are considered. There is still no cure, and treatment strategies are focused on symptoms control. Cell replacement therapies emerge as an alternative. Objective: This review focused on current techniques of induced pluripotent stem cells (iPSCs). Methods: The search terms used were: “Parkinson’s Disease”, “Stem cells” and “iPSC”. Open articles written in English, from 2016-21 were selected in the Pubmed database, 10 publications were identified. Results: With the modernization of iPSC, it was possible to reprogram pluripotent human somatic cells and generate dopaminergic neurons and individual-specific glial cells. To understand the molecular basis, cell and animal models of neurons and organelles are currently being employed. Organoids are derived from stem cells in a three-dimensional matrix, such as matrigel or hydrogels derived from animals. The neuronal models are: α-synuclein (SNCA), leucine-rich repeat kinase2 (LRRK2), PARK2, putative kinase1 induced by phosphatase and tensin homolog (PINK1), DJ-1. Both models offer opportunities to investigate pathogenic mechanisms of PD and test compounds on human neurons. Conclusions: Cell replacement therapy is promising and has great capacity for the treatment of neurodegenerative diseases. Studies using iPSC neuron and PD organoid modeling is highly valuable in elucidating relevants neuronal pathways and therapeutic targets, moreover providing important models for testing future therapies.

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El Nihum, Lamees, Nandan Shettigar, Debjyoti Banerjee, and Robert Krencik. "A Comprehensive Review of Three-Dimensional Neuro-Organoids and Engineering Brain-on-a-Chip Microfluidic Devices." In ASME 2021 Fluids Engineering Division Summer Meeting. American Society of Mechanical Engineers, 2021. http://dx.doi.org/10.1115/fedsm2021-65892.

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Abstract The focus of this review is to describe advances in three-dimensional (3D) organoids reported in the literature with an emphasis on the engineering of microfluidic device platforms for investigating neuro-organoids. Furthermore, the paper will assess current limitations in microfluidic design that must be addressed for realizing the full potential of brain-on-a-chip devices.

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Bahr, AS, M. Simon, D. Capper, et al. "Modeling low-grade glioma with cerebral organoids." In 28th Annual Meeting of the working group “Experimental Neuro-Oncology”. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1696327.

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Ma, Yuanzheng, Davit Khutsishvili, Zitian Wang, Xun Guan, and Shaohua Ma. "Exploring the Neural Organoid in High Definition: Physics-Inspired High-Throughout Super-Resolution 3D Image Reconstruction." In 2023 Asia Communications and Photonics Conference/2023 International Photonics and Optoelectronics Meetings (ACP/POEM). IEEE, 2023. http://dx.doi.org/10.1109/acp/poem59049.2023.10368794.

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