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Articles de revues sur le sujet « Cortical organoids »

Auteur : Grafiati

Publié le 9 mars 2023

Mis à jour le 31 juillet 2025

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1

Bao, Zhongyuan, Kaiheng Fang, Zong Miao, et al. "Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice." Oxidative Medicine and Cellular Longevity 2021 (November 22, 2021): 1–16. http://dx.doi.org/10.1155/2021/6338722.

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Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal c

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Camp, J. Gray, Farhath Badsha, Marta Florio, et al. "Human cerebral organoids recapitulate gene expression programs of fetal neocortex development." Proceedings of the National Academy of Sciences 112, no. 51 (2015): 15672–77. http://dx.doi.org/10.1073/pnas.1520760112.

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Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously u

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Handcock, Sarah, Kay Richards, Timothy J. Karle, et al. "Three-Dimensional Morphological Characterisation of Human Cortical Organoids Using a Customised Image Analysis Workflow." Organoids 4, no. 1 (2025): 1. https://doi.org/10.3390/organoids4010001.

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Summary Statement: A tailored image analysis workflow was applied to quantify cortical organoid health, development, morphology and cellular composition over time. The assessment of cellular composition and viability of stem cell-derived organoid models is a complex but essential approach to understanding the mechanisms of human development and disease. Aim: Our study was motivated by the need for an image-analysis workflow, including high-cell content, high-throughput methods, to measure the architectural features of developing organoids. We assessed stem cell-derived cortical organoids at 4

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Yang, Woo Sub, Ferdi Ridvan Kiral, and In-Hyun Park. "Telencephalic organoids as model systems to study cortical development and diseases." Organoid 4 (January 25, 2024): e1. http://dx.doi.org/10.51335/organoid.2024.4.e1.

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The telencephalon is the largest region of the brain and processes critical brain activity. Despite much progress, our understanding of the telencephalon’s function, development, and pathophysiological processes remains largely incomplete. Recently, 3-dimensional brain models, known as brain organoids, have attracted considerable attention in modern neurobiological research. Brain organoids have been proven to be valuable for studying the neurodevelopmental principles and pathophysiology of the brain, as well as for developing potential therapeutics. Brain organoids can change the paradigm of

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Revah, Omer, Felicity Gore, Kevin W. Kelley, et al. "Maturation and circuit integration of transplanted human cortical organoids." Nature 610, no. 7931 (2022): 319–26. http://dx.doi.org/10.1038/s41586-022-05277-w.

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AbstractSelf-organizing neural organoids represent a promising in vitro platform with which to model human development and disease1–5. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and an

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Farcy, Sarah, Alexandra Albert, Pierre Gressens, Alexandre D. Baffet, and Vincent El Ghouzzi. "Cortical Organoids to Model Microcephaly." Cells 11, no. 14 (2022): 2135. http://dx.doi.org/10.3390/cells11142135.

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How the brain develops and achieves its final size is a fascinating issue that questions cortical evolution across species and man’s place in the animal kingdom. Although animal models have so far been highly valuable in understanding the key steps of cortical development, many human specificities call for appropriate models. In particular, microcephaly, a neurodevelopmental disorder that is characterized by a smaller head circumference has been challenging to model in mice, which often do not fully recapitulate the human phenotype. The relatively recent development of brain organoid technolog

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Bray, Natasha. "Inroads into cortical organoids." Nature Reviews Neuroscience 20, no. 12 (2019): 717. http://dx.doi.org/10.1038/s41583-019-0237-y.

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Conforti, P., D. Besusso, V. D. Bocchi, et al. "Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes." Proceedings of the National Academy of Sciences 115, no. 4 (2018): E762—E771. http://dx.doi.org/10.1073/pnas.1715865115.

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Increasing evidence suggests that early neurodevelopmental defects in Huntington’s disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a large CAG expansion causes complete failure of the neuro-ectodermal acquisition, while cells carrying shorter CAGs repeats show gross abnormalities in neural rosette formation as well as disrupted cytoarchitecture in cortical organ

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Chandrasegaran, Praveena, Agatha Nabilla Lestari, Matthew C. Sinton, Jay Gopalakrishnan, and Juan F. Quintana. "Modelling host-Trypanosoma brucei gambiense interactions in vitro using human induced pluripotent stem cell-derived cortical brain organoids." F1000Research 12 (July 28, 2023): 437. http://dx.doi.org/10.12688/f1000research.131507.2.

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Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and is associated with neuroinflammation and neuropsychiatric disorders, including disruption of sleep/wake patterns, and is now recognised as a circadian disorder. Sleeping sickness is traditionally studied using murine models of infection due to the lack of alternative in vitro systems that fully recapitulate the cellular diversity and functionality of the human brain. The aim of this study is to develop a much-needed in vitro system that reduces and replaces live animals for the study of infections in t

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Li, Xiaodong, Abdullah Shopit, and Jingmin Wang. "A Comprehensive Update of Cerebral Organoids between Applications and Challenges." Oxidative Medicine and Cellular Longevity 2022 (December 5, 2022): 1–10. http://dx.doi.org/10.1155/2022/7264649.

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The basic technology of stem cells has been developed and created organoids, which have established a strong interest in regenerative medicine. Different cell types have been used to generate cerebral organoids, which include interneurons and oligodendrocytes (OLs). OLs are fundamental for brain development. Abundant studies have displayed that brain organoids can recapitulate fundamental and vital features of the human brain, such as cellular regulation and distribution, neuronal networks, electrical activities, and physiological structure. The organoids contain essential ventral brain domain

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Magni, Manuela, Beatrice Bossi, Paola Conforti, et al. "Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models." International Journal of Molecular Sciences 23, no. 21 (2022): 13159. http://dx.doi.org/10.3390/ijms232113159.

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In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal func

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Sivitilli, Adam A., Jessica T. Gosio, Bibaswan Ghoshal, et al. "Robust production of uniform human cerebral organoids from pluripotent stem cells." Life Science Alliance 3, no. 5 (2020): e202000707. http://dx.doi.org/10.26508/lsa.202000707.

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Human cerebral organoid (hCO) models offer the opportunity to understand fundamental processes underlying human-specific cortical development and pathophysiology in an experimentally tractable system. Although diverse methods to generate brain organoids have been developed, a major challenge has been the production of organoids with reproducible cell type heterogeneity and macroscopic morphology. Here, we have directly addressed this problem by establishing a robust production pipeline to generate morphologically consistent hCOs and achieve a success rate of >80%. These hCOs include both a

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Chandrasegaran, Praveena, Agatha Nabilla Lestari, Matthew C. Sinton, Jay Gopalakrishnan, and Juan F. Quintana. "Modelling host-Trypanosoma brucei gambiense interactions in vitro using human induced pluripotent stem cell-derived cortical brain organoids." F1000Research 12 (April 24, 2023): 437. http://dx.doi.org/10.12688/f1000research.131507.1.

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Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and is associated with neuroinflammation and neuropsychiatric disorders, including disruption of sleep/wake patterns, and is now recognised as a circadian disorder. Sleeping sickness is traditionally studied using murine models of infection due to the lack of alternative in vitro systems that fully recapitulate the cellular diversity and functionality of the human brain. The aim of this study is to develop a much-needed in vitro system that reduces and replaces live animals for the study of infections in t

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Rosebrock, Daniel, Sneha Arora, Naresh Mutukula, et al. "Enhanced cortical neural stem cell identity through short SMAD and WNT inhibition in human cerebral organoids facilitates emergence of outer radial glial cells." Nature Cell Biology 24, no. 6 (2022): 981–95. http://dx.doi.org/10.1038/s41556-022-00929-5.

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AbstractCerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early Dual SMAD and WNT inhibition course is necessary and sufficient to establish robust and lasting cortical organoid NSC identity, efficiently suppressing non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC-specification capacity. Accordingly, this method selectively enriches for outer

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Chen, Y., S. Bax, V. Prior, et al. "P12.07.A DEVELOPING NOVEL, MORE STRINGENT EVALUATION PLATFORMS TO ACCELERATE RESEARCH TRANSLATION AND INCREASE SURVIVAL FROM BRAIN CANCER." Neuro-Oncology 26, Supplement_5 (2024): v67. http://dx.doi.org/10.1093/neuonc/noae144.220.

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Abstract BACKGROUND The high grade gliomas (HGG) are a collection of lethal brain tumours. Currently available therapies are unsuccessful and patient survival rates have not significantly improved over the last ~ 50 years. Preclinical models currently in use poorly predict subsequent activity in phase I trials and over-estimate anti-tumour activity in HGG. Fundamental research from many labs, including our own, has shown that the normal tissue environment controls cancer invasion, signalling and response to therapy. Yet most preclinical assays lack this vital element. We have developed a brain

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Forero-Zapata, Laura, Ariel Lee, Alysson Muotri, Cedric Snethlage, Jon A. Gangoiti, and Bruce A. Barshop. "METABOLOMIC STUDIES IN CORTICAL BRAIN ORGANOIDS." Molecular Genetics and Metabolism 135, no. 4 (2022): 271. http://dx.doi.org/10.1016/j.ymgme.2022.01.038.

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Harrison, Charlotte. "Cortical organoids make mouse–human connections." Lab Animal 52, no. 2 (2023): 33. http://dx.doi.org/10.1038/s41684-023-01116-1.

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Marsoner, Fabio, Philipp Koch, and Julia Ladewig. "Cortical organoids: why all this hype?" Current Opinion in Genetics & Development 52 (October 2018): 22–28. http://dx.doi.org/10.1016/j.gde.2018.04.008.

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Shi, Yingchao, Le Sun, Mengdi Wang, et al. "Vascularized human cortical organoids (vOrganoids) model cortical development in vivo." PLOS Biology 18, no. 5 (2020): e3000705. http://dx.doi.org/10.1371/journal.pbio.3000705.

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Qian, Xuyu, Yijing Su, Christopher D. Adam, et al. "Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation." Cell Stem Cell 26, no. 5 (2020): 766–81. http://dx.doi.org/10.1016/j.stem.2020.02.002.

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Kan, Ryan, Weihong Ge, Can Yilgor, et al. "CSIG-15. PTN-PTPRZ1 SIGNALING MEDIATES TUMOR-NORMAL CROSSTALK IN GLIOBLASTOMA." Neuro-Oncology 25, Supplement_5 (2023): v43. http://dx.doi.org/10.1093/neuonc/noad179.0171.

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Abstract Glioblastoma (GBM) is the most devastating form of brain cancer with poor patient prognosis and high recurrence. An increasing body of literature suggests crosstalk between tumor and its surroundings, both molding the immune microenvironment and forming functional synapses with neighboring normal cells. Despite the high intra-tumoral and inter-patient heterogeneity, we have discovered PTN-PTPRZ1 signaling as the most significant and preserved communication pathway between GBM cells and their immediate neighboring cells. Through a novel tumor transplantation protocol onto cortical orga

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Park, Soomin, and Jong-Chan Park. "Advancements in brain organoid models for neurodegenerative disease research." Organoid 4 (December 25, 2024): e12. https://doi.org/10.51335/organoid.2024.4.e12.

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Neurodegenerative diseases (NDs) such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) are progressive disorders characterized by complex, human-specific pathology that poses challenges to drug discovery efforts. Traditional models, including two-dimensional cell cultures and animal models, often fall short in replicating the intricate cellular interactions observed in human neurodegeneration. This review explores the potential of brain organoid technology to address these limitations and offer a model more relevant to humans. Recent advancements in induced pluripotent stem cell (iPSC)

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Santos, Alexandra C., George Nader, Dana El Soufi El Sabbagh, Karolina Urban, Liliana Attisano, and Peter L. Carlen. "Treating Hyperexcitability in Human Cerebral Organoids Resulting from Oxygen-Glucose Deprivation." Cells 12, no. 15 (2023): 1949. http://dx.doi.org/10.3390/cells12151949.

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Human cerebral organoids resemble the 3D complexity of the human brain and have the potential to augment current drug development pipelines for neurological disease. Epilepsy is a complex neurological condition characterized by recurrent seizures. A third of people with epilepsy do not respond to currently available pharmaceutical drugs, and there is not one drug that treats all subtypes; thus, better models of epilepsy are needed for drug development. Cerebral organoids may be used to address this unmet need. In the present work, human cerebral organoids are used along with electrophysiologic

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Ben-Yishay, Rakefet Ruth, Naama Herman, Vered Noy, Eyal Mor, Aiham Mansur, and Dana Ishay-Ronen. "Abstract 5847: Normal mammary epithelium of BRCA1 mutation carriers demonstrates increased susceptibility to cell plasticity." Cancer Research 82, no. 12_Supplement (2022): 5847. http://dx.doi.org/10.1158/1538-7445.am2022-5847.

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Abstract Background: Epithelial-mesenchymal transition (EMT) in breast cancer drives tumor invasion, metastasis and drug resistance. BRCA1 mutation carriers have a high risk for developing aggressive basal-like triple-negative breast cancers with EMT characteristics. It has been described that normal mammary epithelium of BRCA1-mutation carriers is comprised of aberrant luminal progenitor cell population resembling basal-like breast cancer cells. Yet, the role of BRCA1 in regulating epithelial cell plasticity in normal mammary gland remains largely obscure. Aim: Here, we used patient-derived n

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Xiang, Yangfei, Yoshiaki Tanaka, Bilal Cakir, et al. "hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids." Cell Stem Cell 24, no. 3 (2019): 487–97. http://dx.doi.org/10.1016/j.stem.2018.12.015.

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Negatu, Seble, Christine Vazquez, Carl Bannerman, Guo-li Ming, and Kellie Jurado. "Forebrain organoids reveal neuronal capacity to elicit protective antiviral responses." Journal of Immunology 212, no. 1_Supplement (2024): 1176_5399. http://dx.doi.org/10.4049/jimmunol.212.supp.1176.5399.

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Abstract Mosquito-borne arboviruses with potential to cause neurotropic disease are a global health threat. These neurotropic viruses are the most common cause of infectious encephalitis (inflammation of the brain), yet our knowledge of antiviral immune regulation at this site remains limited. Neurons are the highly targeted by these viruses and thus must be important mediators of viral replication and spread. Our studies sought to use La Crosse Virus, an emerging arbovirus, to define intrinsic neuronal orchestration of antiviral responses between infected cells and neighboring uninfected byst

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Atamian, Alexander, Marcella Birtele, and Giorgia Quadrato. "Not all cortical organoids are created equal." Nature Cell Biology 24, no. 6 (2022): 805–6. http://dx.doi.org/10.1038/s41556-022-00890-3.

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Amiri, Anahita, Gianfilippo Coppola, Soraya Scuderi, et al. "Transcriptome and epigenome landscape of human cortical development modeled in organoids." Science 362, no. 6420 (2018): eaat6720. http://dx.doi.org/10.1126/science.aat6720.

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Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progres

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Shnaider, T. A. "Cerebral organoids: a promising model in cellular technologies." Vavilov Journal of Genetics and Breeding 22, no. 2 (2018): 168–78. http://dx.doi.org/10.18699/vj18.344.

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The development of the human brain is a complex multi-stage process including the formation of various types of neural cells and their interactions. Many fundamental mechanisms of neurogenesis have been established due to the studying of model animals. However, significant differences in the brain structure compared to other animals do not allow considering all aspects of the human brain formation, which could play the main role in the development of unique cognitive abilities for human. Four years ago, Lancaster’s group elaborated human pluripotent stem cell-derived three-dimensional cerebral

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López-Tobón, Alejandro, Carlo Emanuele Villa, Cristina Cheroni, et al. "Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis." Stem Cell Reports 13, no. 5 (2019): 847–61. http://dx.doi.org/10.1016/j.stemcr.2019.09.005.

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Hernández, Damián, Duncan E. Crombie, Helena H. Liang, et al. "MODELLING ALZHEIMER’S DISEASE USING HUMAN CORTICAL CEREBRAL ORGANOIDS." Alzheimer's & Dementia 13, no. 7 (2017): P1482—P1483. http://dx.doi.org/10.1016/j.jalz.2017.07.559.

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Pérez-Brangulí, Francesc, Isabel Y. Buchsbaum, Tatyana Pozner, et al. "Human SPG11 cerebral organoids reveal cortical neurogenesis impairment." Human Molecular Genetics 28, no. 6 (2018): 961–71. http://dx.doi.org/10.1093/hmg/ddy397.

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Yi, Sang Ah, Ki Hong Nam, Jihye Yun, et al. "Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus." Viruses 12, no. 9 (2020): 1004. http://dx.doi.org/10.3390/v12091004.

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Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was s

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Prior, Victoria, Simon Maksour, Sara Miellet, et al. "BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING." Neuro-Oncology 25, Supplement_1 (2023): i7. http://dx.doi.org/10.1093/neuonc/noad073.028.

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Abstract Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly brain cancers in children for which there is currently no effective treatment. In part, this can be attributed to preclinical models that lack essential elements of the in vivo tissue environment, resulting in treatments that appear promising preclinically, but fail to result in effective cures. Recently developed co-culture models combining stem cell-derived brain organoids with brain cancer cells provide tissue dimensionality and a human-relevant tissue-like microenvironment. As these models are technically challenging and time co

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Ma, Haihua, Juan Chen, Zhiyu Deng, et al. "Multiscale Analysis of Cellular Composition and Morphology in Intact Cerebral Organoids." Biology 11, no. 9 (2022): 1270. http://dx.doi.org/10.3390/biology11091270.

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Cerebral organoids recapitulate in vivo phenotypes and physiological functions of the brain and have great potential in studying brain development, modeling diseases, and conducting neural network research. It is essential to obtain whole-mount three-dimensional (3D) images of cerebral organoids at cellular levels to explore their characteristics and applications. Existing histological strategies sacrifice inherent spatial characteristics of organoids, and the strategy for volume imaging and 3D analysis of entire organoids is urgently needed. Here, we proposed a high-resolution imaging pipelin

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Cho, Ann-Na, Fiona Bright, Nicolle Morey, Carol Au, Lars M. Ittner, and Yazi D. Ke. "Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus." Cells 11, no. 20 (2022): 3194. http://dx.doi.org/10.3390/cells11203194.

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Cortical organoids are 3D structures derived either from human embryonic stem cells or human induced pluripotent stem cells with their use exploding in recent years due to their ability to better recapitulate the human brain in vivo in respect to organization; differentiation; and polarity. Adeno-associated viruses (AAVs) have emerged in recent years as the vectors of choice for CNS-targeted gene therapy. Here; we compare the use of AAVs as a mode of gene expression in cortical organoids; over traditional methods such as lipofectamine and electroporation and demonstrate its ease-of-use in gene

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Hale, Andrew T., Yuwei Song, and Zechen Chong. "268 Integrative Genomics Identifies Evolutionary, Temporal, and Cell-lineage Origin of Hydrocephalus Risk Gene." Neurosurgery 70, Supplement_1 (2024): 75. http://dx.doi.org/10.1227/neu.0000000000002809_268.

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INTRODUCTION: Our previous work identified MAEL, a gene involved in regulation of DNA transposon activity and histone methylation, as a transcriptome-wide predictor of pediatric hydrocephalus (Hale et al., Cell Reports, 2021). Here we aim to characterize the function of MAEL across timescales and cell-lineages in the developing human brain to understand the pathophysiological basis of hydrocephalus. METHODS: We performed taxonomic analysis of MAEL across species using Ensemble. Analysis of single-cell RNA sequencing (scRNA-seq) of 49 brain regions across the prenatal period from the Developing

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Lim, Bitna, Yurika Matsui, Seunghyun Jung, et al. "Phosphorylation of the DNA damage repair factor 53BP1 by ATM kinase controls neurodevelopmental programs in cortical brain organoids." PLOS Biology 22, no. 9 (2024): e3002760. http://dx.doi.org/10.1371/journal.pbio.3002760.

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53BP1 is a well-established DNA damage repair factor that has recently emerged to critically regulate gene expression for tumor suppression and neural development. However, its precise function and regulatory mechanisms remain unclear. Here, we showed that phosphorylation of 53BP1 at serine 25 by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical brain organoids. Dynamic phosphorylation of 53BP1-serine 25 controls 53BP1 target genes governing neuronal differentiation and function, cellular response to stress, and apoptosis. Mechanistically, ATM an

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Nowakowski, Tomasz J., and Sofie R. Salama. "Cerebral Organoids as an Experimental Platform for Human Neurogenomics." Cells 11, no. 18 (2022): 2803. http://dx.doi.org/10.3390/cells11182803.

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The cerebral cortex forms early in development according to a series of heritable neurodevelopmental instructions. Despite deep evolutionary conservation of the cerebral cortex and its foundational six-layered architecture, significant variations in cortical size and folding can be found across mammals, including a disproportionate expansion of the prefrontal cortex in humans. Yet our mechanistic understanding of neurodevelopmental processes is derived overwhelmingly from rodent models, which fail to capture many human-enriched features of cortical development. With the advent of pluripotent s

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Li, Xiao-Hong, Di Guo, Li-Qun Chen, et al. "Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits." Brain, May 13, 2024. http://dx.doi.org/10.1093/brain/awae150.

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Abstract Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injure

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Bertucci, Taylor, Kathryn Bowles, Steven Lotz, et al. "Human iPSC derived organoid models to study tau pathology." Alzheimer's & Dementia 20, S6 (2024). https://doi.org/10.1002/alz.087353.

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AbstractBackgroundHuman pluripotent stem cell (hPSC)‐derived brain organoids patterned towards the cerebral cortex are valuable models of interactions occurring in vivo in cortical tissue. We and others have used these cortical organoids to model dominantly inherited FTD‐tau. While these studies have provided essential insights, cortical organoid models have yet to reach their full potential. Studies are hindered by well‐recognized hurdles: low production efficiency and high variability between individual organoids, across lines, and experiments. A protocol that consistently generates well‐pat

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Wilson, Madison N., Martin Thunemann, Xin Liu, et al. "Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex." Nature Communications 13, no. 1 (2022). http://dx.doi.org/10.1038/s41467-022-35536-3.

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AbstractHuman cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, match

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Zourray, Clara, Manju A. Kurian, Serena Barral, and Gabriele Lignani. "Electrophysiological Properties of Human Cortical Organoids: Current State of the Art and Future Directions." Frontiers in Molecular Neuroscience 15 (February 16, 2022). http://dx.doi.org/10.3389/fnmol.2022.839366.

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Human cortical development is an intricate process resulting in the generation of many interacting cell types and long-range connections to and from other brain regions. Human stem cell-derived cortical organoids are now becoming widely used to model human cortical development both in physiological and pathological conditions, as they offer the advantage of recapitulating human-specific aspects of corticogenesis that were previously inaccessible. Understanding the electrophysiological properties and functional maturation of neurons derived from human cortical organoids is key to ensure their p

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Cadena, Melissa A., Anson Sing, Kylie Taylor, et al. "A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development." Advanced Healthcare Materials, May 30, 2024. http://dx.doi.org/10.1002/adhm.202401603.

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AbstractThe ability to promote three‐dimensional (3D) self‐organization of induced pluripotent stem cells into complex tissue structures called organoids presents new opportunities for the field of developmental biology. Brain organoids have been used to investigate principles of neurodevelopment and neuropsychiatric disorders and serve as a drug screening and discovery platform. However, brain organoid cultures are currently limited by a lacking ability to precisely control their extracellular environment. Here, we employed 3D bioprinting to generate a high‐throughput, tunable, and reproducib

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Zhang, Xiao-Shan, Gang Xie, Honghao Ma, et al. "Highly reproducible and cost-effective one-pot organoid differentiation using a novel platform based on PF-127 triggered spheroid assembly." Biofabrication, August 8, 2023. http://dx.doi.org/10.1088/1758-5090/acee21.

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Abstract Organoid technology offers sophisticated in vitro human models for basic research and drug development. However, low batch-to-batch reproducibility and high cost due to laborious procedures and materials prevent organoid culture standardization for automation and high-throughput applications. Here, using a novel platform based on the findings that Pluronic F-127 (PF-127) could trigger highly uniform spheroid assembly through a mechanism different from plate coating, we develop a one-pot organoid differentiation strategy. Using our strategy, we successfully generate cortical, nephron,

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Jalilian, Elmira, and Su Ryon Shin. "Novel model of cortical–meningeal organoid co-culture system improves human cortical brain organoid cytoarchitecture." Scientific Reports 13, no. 1 (2023). http://dx.doi.org/10.1038/s41598-023-35077-9.

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AbstractHuman cortical organoids (hCOs), derived from human induced pluripotent stem cells (iPSCs), provide a platform to interrogate mechanisms of human brain development and diseases in complex three- dimensional tissues. However, current hCO development methods lack important non-neural tissues, such as the surrounding meningeal layer, that have been shown to be essential for normal corticogenesis and brain development. Here, we first generated hCOs from a single rosette to create more homogenous organoids with consistent size around 250 µm by day 5. We then took advantage of a 3D co-cultur

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Brown, Rebecca M., Pranav S. J. B. Rana, Hannah K. Jaeger, John M. O’Dowd, Onesmo B. Balemba, and Elizabeth A. Fortunato. "Human Cytomegalovirus Compromises Development of Cerebral Organoids." Journal of Virology 93, no. 17 (2019). http://dx.doi.org/10.1128/jvi.00957-19.

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ABSTRACTCongenital human cytomegalovirus (HCMV) infection causes a broad spectrum of central and peripheral nervous system disorders, ranging from microcephaly to hearing loss. These ramifications mandate the study of virus-host interactions in neural cells. Neural progenitor cells are permissive for lytic infection. We infected two induced pluripotent stem cell (iPSC) lines and found these more primitive cells to be susceptible to infection but not permissive. Differentiation of infected iPSCs inducedde novoexpression of viral antigens. iPSCs can be cultured in three dimensions to generate ce

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Kong, Dasom, Ki Hoon Park, Da-Hyun Kim, et al. "Cortical-blood vessel assembloids exhibit Alzheimer’s disease phenotypes by activating glia after SARS-CoV-2 infection." Cell Death Discovery 9, no. 1 (2023). http://dx.doi.org/10.1038/s41420-022-01288-8.

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AbstractA correlation between COVID-19 and Alzheimer’s disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARS-CoV-2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. Cerebral pericytes and endothelial cells, the major components of blood-brain barrier, express viral entry receptors for SARS-CoV-2 and response to systemic inflammation including direct cell death. To overcome the limitations,

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Harbuzariu, Adriana, Sidney Pitts, Juan Carlos Cespedes, et al. "Modelling heme-mediated brain injury associated with cerebral malaria in human brain cortical organoids." Scientific Reports 9, no. 1 (2019). http://dx.doi.org/10.1038/s41598-019-55631-8.

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AbstractHuman cerebral malaria (HCM), a severe encephalopathy associated with Plasmodium falciparum infection, has a 20–30% mortality rate and predominantly affects African children. The mechanisms mediating HCM-associated brain injury are difficult to study in human subjects, highlighting the urgent need for non-invasive ex vivo human models. HCM elevates the systemic levels of free heme, which damages the blood-brain barrier and neurons in distinct regions of the brain. We determined the effects of heme on induced pluripotent stem cells (iPSCs) and a three-dimensional cortical organoid syste

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Cho, Ann-Na, Yoonhee Jin, Yeonjoo An, et al. "Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids." Nature Communications 12, no. 1 (2021). http://dx.doi.org/10.1038/s41467-021-24775-5.

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AbstractBrain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensio

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