The present invention includes methods and compositions for modifying endothelial cells for improved vascular self-assembly. In some embodiments, the invention includes a modified endothelial cell and methods of generating and using the modified endothelial cell in a pharmaceutical composition. Other embodiments include methods of promoting vascular self-assembly and regenerating vascular structures in a subject in need thereof. In particular, the modified endothelial cell has reduced immunogenicity in an allogeneic environment in the subject, while still capable of forming vascular structures.