Abstract
PurposesThe potent stem cell homing factor stromal cell-derived factor-1 (SDF-1) actively recruits mesenchymal stem cells from circulation and from local bone marrow. It is well established that bone morphogenetic protein-2 (BMP-2) induces ectopic and orthotopic bone formation. However, the exact synergistic effects of BMP-2 and SDF-1 in ectopic and orthotopic bone regeneration models have not been fully investigated. The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation.Materials and MethodsVarious doses of SDF-1 were loaded onto collagen sponges with or without BMP-2.These sponges were implanted into subcutaneous pockets and critical-size calvarial defects in C57BL/6 mice. The specimens were harvested 4 weeks post-surgery and the degree of bone formation in specimens was evaluated by histomorphometric and radiographic density analyses. Osteogenic potential and migration capacity of mesenchymal cells and capillary tube formation of endothelial cells following dual treatment with SDF-1 and BMP-2 were evaluated with in vitro assays.ResultsSDF-1-only-treated implants did not yield significant in vivo bone formation and SDF-1 treatment did not enhance BMP-2-induced ectopic and orthotopic bone regeneration. In vitro experiments showed that concomitant use of BMP-2 and SDF-1 had no additive effect on osteoblastic differentiation, cell migration or angiogenesis compared to BMP-2 or SDF-1 treatment alone.ConclusionsThese findings imply that sequence-controlled application of SDF-1 and BMP-2 must be further investigated for the enhancement of robust osteogenesis in bone defects.
Highlights
Autologous bone grafts in bone defect areas are regarded as a gold-standard therapy in clinical practice
stromal cell-derived factor-1 (SDF-1)-only-treated implants did not yield significant in vivo bone formation and SDF-1 treatment did not enhance bone morphogenetic protein-2 (BMP-2)-induced ectopic and orthotopic bone regeneration
In vitro experiments showed that concomitant use of BMP-2 and SDF-1 had no additive effect on osteoblastic differentiation, cell migration or angiogenesis compared to BMP-2 or SDF-1 treatment alone
Summary
Autologous bone grafts in bone defect areas are regarded as a gold-standard therapy in clinical practice. Because of donor site morbidity caused by the bone harvesting process, implantation of mesenchymal stem cells (MSCs) from bone marrow into bone defect areas has been suggested as an alternative to bone grafts [1]. MSCs can differentiate into various osteoprogenitor cells that can directly form bone structure and indirectly influence bone regeneration by modulating various growth factors and cytokines; the direct use of MSCs for implantation has several limitations. The application of cytokines or growth factors at the site of bone healing and regeneration has been suggested as a means of overcoming the shortcomings of cell therapy [4]. Structurally abnormal bone and tissue inflammatory reactions were observed after applications of high concentrations of BMP-2 [8, 9]
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