Vascularized human brain organoids: current possibilities and prospects

Human brain organoids (hBOs) are in vitro, 3D, self-organizing brain tissue structures increasingly used for modeling brain development and disease. Although they traditionally lack vasculature, recent bioengineering developments enable their vascularization, which partly recapitulates neurodevelopmental processes such as neural tube angiogenesis, formation of neurovascular unit (NVU)-like structures, and early barriergenesis. Although vascularized hBOs (vhBOs) are already used to model (defects in) neurovascular development, vascularization efficiency and other outcomes differ substantially between vascularization protocols and overall shortcomings should be considered. For instance, vessel-like structures in vhBOs do not contain blood-like flow nor do they form a functional blood-brain barrier (BBB). Extended characterization, standardization, and the development of new bioengineering techniques may enable broader applications of vhBOs such as drug transport studies.