Generation of vascularized brain organoids to study neurovascular interactions

TLDR

Brain organoids model brain development, yet their lack of vasculature limits their ability to study neurogenesis and disease. This study seeks to generate vascularized brain organoids by fusing separately induced vessel and brain organoids. The authors induced vessel organoids and brain organoids independently, then fused them to create a composite organoid containing vascular structures. The resulting organoids displayed robust vascular networks, increased neural progenitors, functional blood–brain barrier–like structures, and responsive microglia capable of synaptic engulfment, enabling in‑vitro modeling of neurovascular interactions.

Abstract

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood–brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.