A major challenge in bone tissue engineering is the lack of post-implantation vascular growth into biomaterials. In the skeletal system, blood vessel growth appears to be coupled to osteogenesis-suggesting the existence of molecular crosstalk between endothelial cells (ECs) and osteoblastic cells. The present study (performed in two murine ectopic models) was designed to determine whether co-transplantation of human Wharton's jelly mesenchymal stem cell-derived osteoblasts (WJMSC-OBs) and human differentiated ECs enhances bone regeneration and stimulates angiogenesis, relative to the seeding of WJMSC-OBs alone. Human WJMSC-OBs and human ECs were loaded into a silicate-substituted calcium phosphate (SiCaP) scaffold and then ectopically implanted at subcutaneous or intramuscular sites in nude mice. At both subcutaneous and intramuscular implantation sites, we observed ectopic bone formation and osteoids composed of host cells when WJMSC-OBs were seeded into the scaffold. However, the addition of ECs was associated with a lower level of osteogenesis, and we did not observe stimulation of blood vessel ingrowth. in vitro studies demonstrated that WJMSC-OBs lost their ability to secrete vascular endothelial growth factor and stromal cell-derived factor 1-including when ECs were present. In these two murine ectopic models, our cell-matrix environment combination did not seem to be optimal for inducing vascularized bone reconstruction.