title: The role of endothelial progenitor cells in prevascularized bone tissue engineering: development of heterogeneous constructs.
abstract: 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.
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, The Netherlands.
authors.forename: Natalja E
authors.initials: NE
authors.lastname: Fedorovich
authors.forename: René T
authors.initials: RT
authors.lastname: Haverslag
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Alblas
mesh_terms: D000818:Animals; D001681:Biological Assay; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000098:blood supply* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006041:Goats; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D010012:Osteogenesis / Q000187:drug effects; D011509:Proteoglycans / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen