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; 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.