Effect of Endothelial Differentiated Adipose-Derived Stem Cells on Vascularity and Osteogenesis in Poly (D, L-Lactide) Scaffolds In Vivo.

摘要

Prevascularization of engineered bony constructs can potentially improve in vivo viability. However, the effect of endothelial cells on osteogenesis is unknown when placed in poly(D,L lactide) (PLA) scaffolds alone. Adipose derived stem cells (ASCs) have the ability to differentiate into both osteoblasts and endothelial cells by culture in specific media. We hypothesized that ASC derived endothelial cells would improve vascularity with minimal contribution to bone formation when placed in scaffold alone. ASCs were successfully differentiated into endothelial cells (ASC Endo) and osteoblasts (ASC Osteo) using media supplemented with vascular endothelial growth factor and bone morphogenic protein 2, respectively. Tissue engineered constructs were created with PLA ma trices containing no cells (control), undifferentiated ASCs (ASCs), osteogenic differentiated ASCs (ASC Osteo), or endothelial differentiated ASCs (ASC Endo), and these constructs were evaluated in critical size Lewis rat calvarial defect model (n 34). Eight weeks after implantation, the bone volume and microvessel population of bony constructs were evaluated by micro computed tomography analysis and histologic staining. Bone volumes for ASCs and ASC Osteo constructs, 0.7 and 0.91 mm3, respectively, were statistically greater than that for ASC Endo, 0.28 mm3 (P G 0.05). There was no statistical difference between the PLA control (0.5 mm3) and ASC Endo (0.28 mm3) constructs in bone formation. The percent area of microvessels within constructs was highest in the ASC Endo group, although it did not reach statistical significance (0.065). Prevascularization of PLA scaffold with ASC Endo cells will not increase bone formation by itself but may be used as a cell source for improving vascularization and potentially improving existing osteoblast function.