The vascularization of organoids, a critical aspect of creating physiologically relevant miniature organs, often involves the co-culture with endothelial cells. Endothelial cells are derived from mesoderm and are required for the formation of new blood vessels.
This interaction mirrors the intricate interaction that occurs during embryonic development and early organogenesis, encouraging endothelial cells to self-assemble into capillary-like structures within the organoid.
In the context of human brain organoids, co-culturing with vascular cells, specifically a monolayer of endothelial cells, has been employed to achieve organoid vascularization. In 2018, Pham et al., successfully vascularized 34-day-old human brain organoids by embedding them in Matrigel, enriched with endothelial cells derived from human iPSCs, along with bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor A (VEGF 165), and fibroblast growth factor 2 (FGF-2). After 34 days of co-culture, these brain organoids displayed a network of penetrating vessels expressing platelet endothelial cell adhesion molecule, a key endothelial marker.
Perhaps the most common method for organoid vascularization involves co-culturing human organoids with human umbilical vascular endothelial cells (HUVECs). In brain organoids vascularized through HUVEC co-culture for over 200 days, Shi et al., found that vascularization initially manifests in the ventricular zone (VZ)-like region, which houses neural stem and progenitor cells (NSPCs), mirroring the developmental patterns of the human brain vasculature. Vascularized brain organoids exhibit more robust growth compared to their non-vascularized counterparts, suggesting that vascularization promotes the proliferation of NSPCs and/or the survival of neurons, even in an in vitro environment.