Central nervous system vascularization in human embryos and neural organoids

In recent years, neural organoids derived from human pluripotent stem cells (hPSCs) have offered a transformative pre-clinical platform for understanding central nervous system (CNS) development, disease, drug effects, and toxicology. CNS vasculature plays an important role in all these scenarios; h...

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Published in:Cell reports (Cambridge) 2024-12, Vol.43 (12), p.115068, Article 115068
Main Authors: Boutom, Sarah M., Silva, Teresa P., Palecek, Sean P., Shusta, Eric V., Fernandes, Tiago G., Ashton, Randolph S.
Format: Article
Language:English
Subjects:
angiogenesis
blood-brain barrier
central nervous system
Central Nervous System - blood supply
CP: Stem cell research
Embryo, Mammalian
endothelium
human pluripotent stem cell
Humans
microphysiological system
Neovascularization, Physiologic
neural rosette
neuroepithelium
neurogenesis
neurovascular unit
organoid
Organoids - blood supply
perineural vascular plexus
periventricular plexus
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
vasculogenesis
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Summary:In recent years, neural organoids derived from human pluripotent stem cells (hPSCs) have offered a transformative pre-clinical platform for understanding central nervous system (CNS) development, disease, drug effects, and toxicology. CNS vasculature plays an important role in all these scenarios; however, most published studies describe CNS organoids that lack a functional vasculature or demonstrate rudimentary incorporation of endothelial cells or blood vessel networks. Here, we review the existing knowledge of vascularization during the development of different CNS regions, including the brain, spinal cord, and retina, and compare it to vascularized CNS organoid models. We highlight several areas of contrast where further bioengineering innovation is needed and discuss potential applications of vascularized neural organoids in modeling human CNS development, physiology, and disease. Human pluripotent stem cell-derived neural organoids are promising models for studying central nervous system development and disease. However, few have successfully been vascularized, and none truly recapitulate in vivo vascularization patterns. Here, developmental anatomy and bioengineering principles are discussed to chart a path toward enhancing vascularized neural organoid biomimicry.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2024.115068