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Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.
Cerebral organoids are complex, three-dimensional (3D) dynamic models that recapitulate key features of brain development and disease. These systems serve as bioengineerable platforms with diverse architectures and customizable properties, enabling advances in both basic and translational neuroscience. Despite rapid adoption across neurodevelopment, neurodegeneration, and neuro-oncology, the field remains fragmented, with substantial methodological variability and no standardized framework for model selection. A systematic review of 738 original studies published between 2014 and 2024, drawn from 3631 articles across PubMed, Semantic Scholar, and OpenAlex, reveals that human induced pluripotent stem cell-derived cerebral organoids and neurodevelopmental studies dominate the field. In contrast, applications in neurodegeneration, brain metastases, and non-human systems remain limited, narrowing the translational scope. To address the challenge of navigating this expanding literature, OrganoidMap is introduced-an open-access, interactive web platform for exploring, filtering, and comparing cerebral organoid models across disease areas, cell sources, and methodological features. OrganoidMap enables the identification of appropriate models for specific experimental goals and reveals underexplored research areas. This synthesis establishes a scalable foundation for enhancing transparency, reproducibility, and model selection in organoid-based research, setting a new benchmark for how neuroscience and biomaterials communities organize, share, and advance cerebral organoid science.
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Quantitative and Qualitative Analysis of Neurotransmitter and Neurosteroid Production in Cerebral Organoids during Differentiation.
In the human brain, neurophysiological activity is modulated by the movement of neurotransmitters and neurosteroids. To date, the similarity between cerebral organoids and actual human brains has been evaluated using comprehensive multiomics approaches. However, a systematic analysis of both neurotransmitters and neurosteroids from cerebral organoids has not yet been reported. Here, we performed quantitative and qualitative assessments of neurotransmitters and neurosteroids over the course of cerebral organoid differentiation. Our multiomics approaches revealed that the expression levels of neurotransmitter-related proteins and RNA, including neurosteroids, increase as cerebral organoids mature. We also found that the electrophysiological activity of human cerebral organoids increases in tandem with the expression levels of both neurotransmitters and neurosteroids. Our study demonstrates that the expression levels of neurotransmitters and neurosteroids can serve as key factors in evaluating the maturity and functionality of human cerebral organoids.
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What Brain Organoid Research Can Gain From Engaging Biospecimen Donors.
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Self-organized developmental patterning and differentiation in cerebral organoids.
Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso-ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulated in vitro.
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Protocol for human brain organoid transplantation into a rat visual cortex to model neural repair.
Human stem-cell-derived organoids represent a promising substrate for transplantation-based neural repair. Here, we describe a protocol for transplanting forebrain organoids into an injured adult rat visual cortex. This protocol includes surgical details for craniectomy, aspiration injury, organoid transplantation, and cranioplasty. This platform represents a valuable tool for investigating the efficacy of organoids as structured grafts for neural repair. For complete details on the use and execution of this protocol, please refer to Jgamadze et al.1.
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Mapping the Evolution of Brain Organoid Research: A Decade of Progress and Future Perspectives (2015-2025).
Brain organoids have revolutionized neuroscience by providing unique in vitro models for studying human brain development and disease. This study presents a comprehensive bibliometric analysis of brain organoid research from 2015 to 2025, integrating VOSviewer and CiteSpace, while using Scimago Graphica to enhance the visualization. Our journal analysis reveals Stem Cell Reports and Cell Stem Cell as stable high-impact venues, with Stem Cell Reports and Nature Communications showing the fastest growth. Geographically, the USA and European nations maintain dominance in both productivity and citation impact. We systematically mapped the field's evolution across three phases: the technological germination period (2001-2014), rapid expansion from foundation to application (2015-2020), and recent developments including refinement and ethical considerations (2020-2025). Our analysis reveals key factors contributing to the field's recent cooling trend, including standardization challenges, diversification trends, and emerging ethical concerns. We identify major research hotspots such as vascularization and microenvironment optimization and also highlight critical milestones such as the development of fused organoid systems and vascularized models. This study not only provides a historical perspective on brain organoid research but also offers valuable insights for future directions, emphasizing the need for standardized protocols, enhanced international and multidisciplinary collaboration, and balanced ethical frameworks to sustain progress in this transformative field.
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Pluripotent stem cells for target organ developmental toxicity testing.
Prenatal developmental toxicity research focuses on understanding the potential adverse effects of environmental agents, drugs, and chemicals on the development of embryos and fetuses. Traditional methods involve animal testing, but ethical concerns and the need for human-relevant models have prompted the exploration of alternatives. Pluripotent stem cells (PSCs) are versatile cells with the unique ability to differentiate into any cell type, serving as a foundational tool for studying human development. Two-dimensional (2D) PSC models are often chosen for their ease of use and reproducibility for high-throughput screening. However, they lack the complexity of an in vivo environment. Alternatively, three-dimensional (3D) PSC models, such as organoids, offer tissue architecture and intercellular communication more reminiscent of in vivo conditions. However, they are complicated to produce and analyze, usually requiring advanced and expensive techniques. This review discusses recent advances in the use of human PSCs differentiated into brain and heart lineages and emerging tools and methods that can be combined with PSCs to help address important scientific questions in the area of developmental toxicology. These advancements and new approach methods align with the push for more relevant and predictive developmental toxicity assessment, combining innovative techniques with organoid models to advance regulatory decision-making.
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Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology.
Understanding the complexities of the human brain development remains one of the most formidable challenges in neuroscience, constrained by the limitations of traditional models and the inaccessibility of brain tissue. The advent of cerebral organoids has provided a transformative in vitro model that closely mimics the early stages of brain development, including the spatiotemporal organization and cellular heterogeneity. Derived from pluripotent stem cells, these self-assembling three-dimensional structures address critical limitations of earlier systems, including species-specific differences in animal studies and the structural constraints of conventional cell models. Over the past decade, cerebral organoids have enabled significant advances in studying neural development, neurogenesis, modeling neuroconnectivity, and investigating neuroregeneration. Meanwhile, high-throughput spatial multi-omics technologies have emerged for decoding molecular and cellular dynamics with spatial precision. These techniques retain the architectural context of biological samples while integrating diverse layers of omic information, providing unprecedented insights into tissue organization and interactions. By addressing the complexity of brain organization and facilitating actionable insights into neurodevelopmental diseases, this integration facilitates high-throughput drug screening, identifies disease-specific targets, and offers a path to novel therapeutic strategies and regenerative solution for future stem cell therapies for pediatric neurodevelopmental diseases.
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Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models.
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 function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.
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Evaluating neuroprivacy concerns in human brain organoid research.
Neuroprivacy, or the privacy of neural data, has attracted considerable interest. Here, we explore the implications of neuroprivacy in human brain organoid research, detailing different interpretations of this right. Findings suggest a limited connection between neuroprivacy and brain organoid research, underscoring the importance of further examination of this critical issue.