Abstract
Introduction
Nonunion is a common and costly fracture outcome. Intricate reciprocity between angiogenesis and osteogenesis means vascular cell-based therapy offers a novel approach to stimulating bone regeneration.
Hypothesis
The current study compared early and late outgrowth endothelial progenitor cell subtypes (EPCs vs OECs) for fracture healing potential in vitro and in vivo.
Methods
Primary cell cultures were isolated and characterized by endothelial assays, immunosorbent assays, and multi-color flow cytometry. Co-cultures of EPC subtypes with/without primary osteoblasts (pObs) were analyzed for tube length and connectivity. In vivo, EPCs or OECs (1×106) seeded on a gelfoam scaffold were implanted in a rat model of nonunion. Radiography was used to monitor callus formation.
Results
OECs expressed more BMP-2 and less VEGF than EPCs (p<0.05). Analysis of surface markers showed decreased CD34+/CD133+/Flk-1+, CD133+ and CD45+ populations in OECs while CD34+/CD31+/Flk-1+ cells increased. pObs significantly inhibited the strong tubulogenesis of OECs while enhancing connectivity and sprout length of EPCs. In vivo, 0/6 scaffold-control and 1/5 OEC rats achieved union at 10 weeks. In comparison, all EPC rats achieved full or partial union.
Discussion and Conclusion
Despite favorable tubulogenic and osteoconductive profiles of OECs, EPCs display enhanced fracture healing in vivo. Differences in CXCR4 expression and cell-mediated effects may contribute to this result.
