Human brain organoids are three-dimensional tissues that are generated in vitro from pluripotent stem cells and recapitulate the early development of the human brain. Brain organoids consist mainly of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes, and oligodendrocytes. However, all human brain organoids lack vasculature, which plays indispensable roles not only in brain homeostasis but also in brain development. In addition to the delivery of oxygen and nutrition, accumulating evidence suggests that the vascular system of the brain regulates neural differentiation, migration, and circuit formation during development. Therefore, vascularization of human brain organoids is of great importance. Current trials to vascularize various organoids include the adjustment of cultivation protocols, the introduction of microfluidic devices, and the transplantation of organoids into immunodeficient mice. In this review, we summarize the efforts to accomplish vascularization and perfusion of brain organoids, and we discuss these attempts from a forward-looking perspective.
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http://dx.doi.org/10.1002/stem.3368 | DOI Listing |
Neuron
January 2025
Department of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:
Writing in Neuron, Zhang et al. identify a subpopulation of glioblastoma cells from patient tumor samples with progenitor-like features that expresses the potassium ion channel KCND2. In mouse and organoid models, these cells enhance neural activity at the glioma-neural interface.
View Article and Find Full Text PDFExpert Rev Mol Med
January 2025
Centre for Gene Therapy and Regenerative Medicine, King's College London, London, United Kingdom.
Background: Glioblastoma multiforme (GBM) is the most prevalent primary brain tumour, with an incidence of 2 per 100,000. The standard clinical treatments do not sufficiently target cell migration and invasion, leading to recurrence after surgical resection and resistance after chemotherapy and radiotherapy. Pre-clinical studies are being conducted to construct artificial substrates that can mimic the tumour microenvironment (TME) to prevent GBM cells from migrating along their primary route through blood vessels and white matter tracts.
View Article and Find Full Text PDFToxicol Appl Pharmacol
January 2025
Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States of America. Electronic address:
Modeling brain development and function is challenging due to complexity of the organ. Human pluripotent stem cell (PSC)-derived brain-like organoids provide new tools to study the human brain. Compared with traditional in vivo toxicological studies, these 3D models, together with 2D cellular assays, enhance our understanding of the mechanisms of developmental neurotoxicity (DNT) during the early stages of neurogenesis and offer numerous advantages including a rapid, cost-effective approach for understanding compound mechanisms and assessing chemical safety.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
A cell fate change such as tumorigenesis incurs critical transition. It remains a longstanding challenge whether the underlying mechanism can be unraveled and a molecular switch that can reverse such transition is found. Here a systems framework, REVERT, is presented with which can reconstruct the core molecular regulatory network model and a reversion switch based on single-cell transcriptome data over the transition process is identified.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO, 63110, USA.
Glioblastoma (GBM) is an aggressive form of brain cancer that is highly resistant to therapy due to significant intra-tumoral heterogeneity. The lack of robust in vitro models to study early tumor progression has hindered the development of effective therapies. Here, this study develops engineered GBM organoids (eGBOs) harboring GBM subtype-specific oncogenic mutations to investigate the underlying transcriptional regulation of tumor progression.
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