Aim: We investigated the role of induced endothelial cells (iECs) in mesenchymal stem cells (MSCs)/iECs co-culture and assessed their osteogenic ability on silk fibroin nanofiber scaffolds. Methods: The osteogenic differentiation was assessed by the ALP assay, calcium assay and gene expression studies. Results: The osteogenic differentiation of the iECs co-cultures was found to be higher than the MSCs group and proximal to endothelial cells (ECs) co-cultures. Furthermore, the usage of isogenic iECs for co-culture increased the osteogenic and endothelial gene expression. Conclusion: These findings suggest that iECs mimic endothelial cells when co-cultured with MSCs and that one MSCs source can be used to give rise to both MSCs and iECs. The isogenic MSCs/iECs co-culture provides a new option for bone tissue engineering applications. © 2019 Srinivas Madduri.