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Human brain organoid:trends,evolution,and remaining challenges

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Neural Regeneration Research 2024年第11期19卷 2387-2399页

作者： Minghui Li Yuhan Yuan Zongkun Hou Shilei Hao Liang Jin Bochu Wang Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqingChina Southwest Hospital/Southwest Eye Hospital Third Military Medical University(Army Medical University)ChongqingChina School of Biology and Engineering/School of Basic Medical Sciences Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases.Although various studies and reviews have described developments and advancements in brain organoids,few studies have comprehensively summarized and analyzed the global trends in this area of neuroscience.To identify and further facilitate the development of cerebral organoids,we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 years.First,annual publications,countries/regions,organizations,journals,authors,co-citations,and keywords relating to brain organoids were identified.The hotspots in this field were also systematically identified.Subsequently,current applications for brain organoids in neuroscience,including human neural development,neural disorders,infectious diseases,regenerative medicine,drug discovery,and toxicity assessment studies,are comprehensively discussed.Towards that end,several considerations regarding the current challenges in brain organoid research and future strategies to advance neuroscience will be presented to further promote their application in neurological research.

关键词： bibliometric analysis brain organoids cerebral organoids global trends neuroscience

Modeling human neurodevelopmental diseases with brain organoids

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Cell Regeneration 2022年第1期11卷 1-13页

作者： Xiaoxiang Lu Jiajie Yang Yangfei Xiang School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

Studying the etiology of human neurodevelopmental diseases has long been a challenging task due to the brain’s complexity and its limited accessibility.Human pluripotent stem cells(hPSCs)-derived brain organoids are capable of recapitulating various features and functionalities of the human brain,allowing the investigation of intricate patho-genesis of developmental abnormalities.Over the past years,brain organoids have facilitated identifying disease-associated phenotypes and underlying mechanisms for human neurodevelopmental diseases.Integrating with more cutting-edge technologies,particularly gene editing,brain organoids further empower human disease modeling.Here,we review the latest progress in modeling human neurodevelopmental disorders with brain organoids.

关键词： brain organoids Neurodevepmental diseases Disease modeling Stem cells Gene editing

Neural lineage differentiation of human pluripotent stem cells:Advances in disease modeling

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World Journal of Stem Cells 2023年第6期15卷 530-545页

作者： Yuan-Wei Yan Eddie S Qian Lauren E Woodard Julie Bejoy Waisman Center University of Wisconsin-MadisonMadisonWI 53705United States Nephrology and Hypertension Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Medicine Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Veterans Affairs Tennessee Valley Healthcare SystemNashvilleTN 37232United States Biomedical Engineering Vanderbilt UniversityNashvilleTN 37232United States

brain diseases affect 1 in 6 people worldwide.These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer’s disease.Recent advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models,tissue culture models,and epidemiologic patient data that are commonly used to study brain disease.One innovative method by which to model human neurological disease is via the directed differentiation of human pluripotent stem cells(hPSCs)to neural lineages including neurons,astrocytes,and oligodendrocytes.Three-dimensional models such as brain organoids have also been derived from hPSCs,offering more physiological relevance due to their incorporation of various cell types.As such,brain organoids can better model the pathophysiology of neural diseases observed in patients.In this review,we will emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models.

关键词： Induced pluripotent stem cells Astrocytes Oligodendrocytes Microglia brain organoids Assembloids

Human stem cell modeling of neuropsychiatric disorders:from polygenicity to convergence

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Medical Review

Medical Review 2023年第4期3卷 347-350页

作者： Jubao Duan Center for Psychiatric Genetics NorthShore University Health System Research InstituteEvanston 60201ILUSA Department of Psychiatry and Behavioral Neuroscience The University of ChicagoChicago 60637ILUSA

Neuropsychiatric disorders(NPD)are prevalent and devastating,posing an enormous socioeconomic burden to modern society.Recent genetic studies of NPD have identified a plethora of common genetic risk variants with small effect sizes and rare risk variants of high penetrance.While exciting,there is a pressing need to translate these genetic discoveries into better understanding of disease biology and more tailored clinical interventions.Human induced pluripotent stem cell(hiPSC)-derived 2D and 3D neural cultures are becoming a promising cellular model for bridging the gap between genetic findings and disease biology for NPD.Leveraging the accessibility of patient biospecimen to convert into stem cells and the power of genome editing technology to engineer disease risk variants,hiPSC model holds the promise to disentangle the disease polygenicity,model genetic interaction with environmental factors,and uncover convergent gene pathways that may be targeted for more tailored clinical intervention.

关键词： brain organoids genomics induced neurons induced pluripotent stem cell neuropsychiatric disorder

Human brain organoids on a Chip as a Model for Neurodevelopmental Diseases

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Human Brain Organoids on a Chip as a Model for Neurodevelopm...

Engineering human pluripotent stem cell-derived 3D brain tissues for drug discovery

中国神经科学学会第十二届全国学术会议

作者： Eyal Karzbrun Orly Reiner Department of Molecular Genetics Weizmann Institute of Science

The origin of human brain wrinkling remains an open fundamental problem, with implications to neurodevelopmental disorders. Physical studies in polymer gel models3 suggest wrinkling emerge spontaneously due to development of compression forces during differential growth of cell layers, however biological evidence is limited. Here, we report the emergence of surface wrinkles during in vitro development of human brain organoids, in a micro-fabricated compartment, which supports in situ imaging at subcellular resolution over weeks. The folding dynamics and morphology exhibit similarity to folding in vivo. By studying the cellular dynamics, we observe nuclei compression during development, and the emergence of convolutions at a critical cell density. We identify two opposing forces, which contribute to differential growth: cytoskeleton contraction at the organoid core, and nuclear expansion during cell-cycle at the organoid perimeter. The wrinkling wavelength exhibits linear scaling with tissue thickness, consistent with polymer physics. Remarkably, lissencephalic（smooth brain） organoids exhibited reduced convulsions, linear scaling with an increased prefactor, and reduced elastic modulus. Our results support a physical mechanism for lissencephaly, in which change in tissue elasticity results in reduced folding.

关键词： brain development brain organoids live imaging

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Journal of Translational Neuroscience 2016年第2期1卷 38-48页

作者： Ha Nam Nguyen HongjunSong Guoli Ming Institute for Cell Engineering Johns Hopkins University School of MedicineBaltimoreMD21205USA Department of Neurology Johns Hopkins University School of MedicineBaltimoreMD21205USA The Solomon H Snyder Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMD21205USA Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of MedicineBaltimoreMD21205USA

Abstract The quest to find novel therapeutics for mental and neurological disorders has been hindered by the lack of access to live human brain samples and relevant experimental models. Conventional 2D human pluripotent stem cell-derived neuronal cultures and animal models do not fully recapitulate many endogenous human biochemical processes and diseasephenotypes. Currently, the majority of candidate drugs obtained from preclinical testing in conventional systemsdoes not usually translate into success and have a high failure rate in clinical trials. Recent advancements in bioengineering and stem cell technologies have resulted in three-dimensional brain-like tissues, such as oragnoids,which better resemble endogenous tissue and are morephysiologically relevant than monolayer cultures. These brain-like tissues can bridge the gap between existing models and the patient, and may revolutionize the field of translational neuroscience. Here, we discuss utilities and challenges of using stem cell-derived human braintissues in basic research and pharmacotherapy

关键词： stem cell-derived brain tissues three-threedimensional(3D) translational neuroscience brain organoids stem cell-derived brain tissues three-threedimensional(3D) translational neuroscience brain organoids