Vascular organoids recover blood flow in vivo

Developing vascular organoids (VOs) that faithfully mimic human blood vessels is difficult because both endothelial and mural cells need to be co-differentiated and stably maintained in an organized structure. Existing models offer limited control over cellular composition and incomplete maturation. Now, in Cell Stem Cell, Gong et al. describe a protocol to generate functional VOs in 5 days that engraft in vivo, which provides potential clinical utility.

Building on previously developed protocols, the authors created VOs by transiently activating the transcription factors (TFs) ETV2 and NKX3.1 to enable the co-differentiation of an endothelial and a mural compartment from induced pluripotent stem cells. By expressing the TFs using chemically modified mRNA, the VOs could be produced without a genetic footprint. Although VOs did not need exogenous extracellular matrix to grow, embedding them in hydrogel led to enhanced vascular maturation that resulted in the formation of larger, structured vessels. Single-cell transcriptomics showed that VOs contained heterogeneous vascular cell populations, and changing the duration of TF activation could influence endothelial phenotypes.