Shaping the Neurovascular Unit Exploiting Human Brain Organoids

• Published in: Molecular neurobiology Vol. 61; no. 9; pp. 6642 - 6657
• Main Authors: Rizzuti, Mafalda, Melzi, Valentina, Brambilla, Lorenzo, Quetti, Lorenzo, Sali, Luca, Ottoboni, Linda, Meneri, Megi, Ratti, Antonia, Verde, Federico, Ticozzi, Nicola, Comi, Giacomo Pietro, Corti, Stefania, Abati, Elena
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-09-2024; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain; Brain - blood supply; Cell Biology; Cell differentiation; Cell migration; Humans; Microenvironments; Microfluidics; Neural stem cells; Neurobiology; Neurodevelopmental disorders; Neurological diseases; Neurology; Neurosciences; Organoids; Organoids - cytology; Organoids - physiology; Pluripotency; Reviews; Vascular system; Vascularization; Vascular organoids; Microcirculation; Vascular system; Pluripotent stem cells; Circulation; Cerebral organoids
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-024-03998-9

Brain organoids, three-dimensional cell structures derived from pluripotent stem cells, closely mimic key aspects of the human brain
in vitro
, providing a powerful tool for studying neurodevelopment and disease. The neuroectodermal induction protocol employed for brain organoid generation primarily gives rise to the neural cellular component but lacks the vital vascular system, which is crucial for the brain functions by regulating differentiation, migration, and circuit formation, as well as delivering oxygen and nutrients. Many neurological diseases are caused by dysfunctions of cerebral microcirculation, making vascularization of human brain organoids an important tool for pathogenetic and translational research. Experimentally, the creation of vascularized brain organoids has primarily focused on the fusion of vascular and brain organoids, on organoid transplantation
in vivo
, and on the use of microfluidic devices to replicate the intricate microenvironment of the human brain
in vitro
. This review summarizes these efforts and highlights the importance of studying the neurovascular unit in a forward-looking perspective of leveraging their use for understanding and treating neurological disorders.
Graphical Abstract