The Role of Endothelial Progenitor Cells in Prevascularized Bone Tissue Engineering: Development of Heterogeneous Constructs

• Published in: Tissue engineering. Part A 2010-07, Vol.16 (7), p.2355-2367
• Main Authors: Fedorovich, Natalja E., Haverslag, René T., Dhert, Wouter J.A., Alblas, Jacqueline
• Format: Article
• Language: English
• Subjects: Animals; Biological Assay; Biomarkers - metabolism; Bone and Bones - blood supply; Bone and Bones - drug effects; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone-grafting; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell Separation; Coculture Techniques; Collagen - pharmacology; Colony-Forming Units Assay; Drug Combinations; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium; Goats; Growth; Humans; Laminin - pharmacology; Methods; Mice; Mice, Nude; Neovascularization, Physiologic; Original Articles; Osteogenesis - drug effects; Properties; Proteoglycans - pharmacology; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds - chemistry
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2009.0603

In vitro prevascularization of bone grafts with endothelial progenitor cells (EPCs) is a promising strategy to improveimplant survival. In this study we show bone formation in constructs that contain multipotent stromal cells (MSCs) and EPCs. Early and late EPCs from peripheral blood and bone marrow of adult goats were characterized for differentiation markers and functional responses. EPCs from peripheral blood are more proliferative than bone-marrow-derived EPCs, express higher numbers of endothelial markers for longer periods of time, and form more intricate networks. We demonstrate that EPCs derived from peripheral blood contribute to osteogenic differentiation by MSCs in vitro , and that MSCs support the proliferation of EPCs and stabilize the formed cellular networks. In vivo , EPCs from peripheral blood assemble into early blood vessel networks, which are more pronounced in the presence of MSCs. These results show that the EPCs isolated from peripheral blood are suitable for prevascularization strategies, and that coseeding of EPCs and MSCs is favorable for bone formation after 6 weeks.