Maturation and circuit integration of transplanted human cortical organoids

Nature, Journal Year: 2022, Volume and Issue: 610(7931), P. 319 - 326

Published: Oct. 12, 2022

Abstract Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease 1–5 . However, lack the connectivity that exists vivo, limits maturation makes integration other circuits control behaviour impossible. Here we show stem cell-derived cortical transplanted into somatosensory cortex of newborn athymic rats develop mature cell types integrate sensory motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple lines animals, whereas single-nucleus profiling shows progression corticogenesis emergence activity-dependent transcriptional programs. Indeed, neurons display more complex morphological, synaptic intrinsic membrane properties than their counterparts, enables discovery defects derived from individuals Timothy syndrome. Anatomical functional tracings receive thalamocortical corticocortical inputs, vivo recordings activity demonstrate these inputs can produce responses cells. Finally, extend axons throughout rat brain optogenetic activation drive reward-seeking behaviour. Thus, engage host We anticipate this approach will be useful for detecting circuit-level phenotypes patient-derived cells cannot otherwise uncovered.

Language: Английский

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Human brain organogenesis: Toward a cellular understanding of development and disease

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 42 - 61

Published: Nov. 11, 2021

Language: Английский

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Human cerebral organoids — a new tool for clinical neurology research

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(11), P. 661 - 680

Published: Oct. 17, 2022

Language: Английский

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Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish

Frontiers in Science, Journal Year: 2023, Volume and Issue: 1

Published: Feb. 28, 2023

Recent advances in human stem cell-derived brain organoids promise to replicate critical molecular and cellular aspects of learning memory possibly cognition vitro . Coining the term “organoid intelligence” (OI) encompass these developments, we present a collaborative program implement vision multidisciplinary field OI. This aims establish OI as form genuine biological computing that harnesses using scientific bioengineering an ethically responsible manner. Standardized, 3D, myelinated can now be produced with high cell density enriched levels glial cells gene expression for learning. Integrated microfluidic perfusion systems support scalable durable culturing, spatiotemporal chemical signaling. Novel 3D microelectrode arrays permit high-resolution electrophysiological signaling recording explore capacity recapitulate mechanisms formation and, ultimately, their computational potential. Technologies could enable novel biocomputing models via stimulus-response training organoid-computer interfaces are development. We envisage complex, networked whereby connected real-world sensors output devices, ultimately each other sensory organ (e.g. retinal organoids), trained biofeedback, big-data warehousing, machine methods. In parallel, emphasize embedded ethics approach analyze ethical raised by research iterative, manner involving all relevant stakeholders. The many possible applications this urge strategic development discipline. anticipate OI-based allow faster decision-making, continuous during tasks, greater energy data efficiency. Furthermore, “intelligence-in-a-dish” help elucidate pathophysiology devastating developmental degenerative diseases (such dementia), potentially aiding identification therapeutic approaches address major global unmet needs.

Language: Английский

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Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(8), P. 1197 - 1212.e8

Published: Aug. 1, 2022

Language: Английский

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Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3770 - 3788.e27

Published: Sept. 1, 2022

Language: Английский

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Challenges of Organoid Research

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 23 - 39

Published: Jan. 5, 2022

Organoids are 3D cell culture systems derived from human pluripotent stem cells that contain tissue resident types and reflect features of early organization. Neural organoids a particularly innovative scientific advance given the lack accessibility developing brain intractability neurological diseases. have become an invaluable approach to model development not well reflected in animal models. also hold promise for study atypical cellular, molecular, genetic underscore Additionally, may provide platform testing therapeutics potential source replacement approaches injury or disease. Despite promising organoids, their broad utility is tempered by variety limitations yet be overcome, including high-fidelity types, limited maturation, physiology, arealization, limit reliability certain applications.

Language: Английский

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An in vivo neuroimmune organoid model to study human microglia phenotypes

Cell, Journal Year: 2023, Volume and Issue: 186(10), P. 2111 - 2126.e20

Published: May 1, 2023

Language: Английский

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Human organoids: New strategies and methods for analyzing human development and disease

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2756 - 2769

Published: July 1, 2022

For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this allowed researchers to understand many biological processes great detail, some developmental mechanisms have proven difficult study due inherent species differences. The advent organoid technology more than 10 years ago established laboratory-grown organ tissues as an additional model system recapitulate human-specific aspects biology. use 3D organoids, well other advances single-cell technologies, revealed unprecedented insights mechanisms, especially those that distinguish humans from species. This review highlights novel with a focus on how generated better understanding development disease.

Language: Английский

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Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(22), P. 16839 - 16909

Published: Sept. 15, 2022

Microfluidics has recently emerged as a powerful tool in generation of submillimeter-sized cell aggregates capable performing tissue-specific functions, so-called microtissues, for applications drug testing, regenerative medicine, and therapies. In this work, we review the most recent advances field, with particular focus on formulation cell-encapsulating microgels small "dimensionalities": "0D" (particles), "1D" (fibers), "2D" (sheets), etc., nontrivial internal topologies, typically consisting multiple compartments loaded different types cells and/or biopolymers. Such structures, which refer to topological hydrogels or (examples including core–shell Janus microbeads microfibers, hollow porous microstructures, granular hydrogels) can be precisely tailored high reproducibility throughput by using microfluidics used provide controlled "initial conditions" proliferation maturation into functional tissue-like microstructures. Microfluidic methods biomaterials have enabled significant progress engineering miniature tissues organs, such pancreas, liver, muscle, bone, heart, neural tissue, vasculature, well fabrication microenvironments stem-cell expansion differentiation, cancer modeling, vascularized tumors personalized testing. We available microfluidic exploiting various cross-linking mechanisms routes toward compartmentalization critically discuss applications. Finally, list remaining challenges simplification workflow its widespread use biomedical research, bench-to-bedside transition production upscaling, further vivo validation, more precise organ-like models, incorporation induced pluripotent stem step clinical

Language: Английский

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