This study investigated the cotransplantation of bone marrow mesenchymal stromal cells (BMSC) and human umbilical cord endothelial cells (HUVEC), and evaluated their contribution to vascular and bone tissue engineering in vivo. To evaluate the success of osteogenic differentiation and timely vascularization of different osteoconductive scaffolds in vivo, we transferred BMSC and HUVEC pre-cultivated calcium carbonate (CaCO) and hydroxylapatite (HA) matrices into immunocompromised RNU-rats, and analyzed mineralization, expression of osteopontin, and vascular integration via new vessel formation. After in vivo transplantation, pre-cultivated scaffolds demonstrated overall improved mineralization of 44% for CaCO (p = 0.01, SD ± 14.3) and 34% for HA (p = 0.001, SD ± 17.8), as well as improved vascularization of 5.6 vessels/0.1 mm on CaCO (p < 0.0001, SD ± 2.0) and 5.3 vessels/0.1 mm on HA (p < 0.0001, SD ± 2.4) compared with non-pre-cultivated controls. However, no significant differences between the implantation of BMSC-only, HUVEC-only, or BMSC + HUVEC cocultures could be observed. There is an increasing demand for improved bone regeneration in tissue engineering. Cotransplantation of mesenchymal stromal cells and endothelial cells often demonstrates synergistic improvements in vitro. However, the benefits or superiority of cotransplantation was not evident in vivo and so will require further investigation.

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