Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume

Abstract

Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cellseeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation.We conclude that the addition of stromal cellderived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.

A New Anabolic compound, LLP2A-Ale, Reserves Periodontal Bone Loss in Mice Through Augmentation of Bone Formation

“…These immune cells, in turn, produce various in ammatory cytokines that are thought to be primarily produced by leukocytes, including IL-1, IL-6, IL-7, IL-17, and TNF-α, which defend against bacterial infection but may indirectly stimulate osteoclastogenesis and bone resorption. Other cytokines, such as CXCL10, CXCL12, CXCL13, and CCL5, may affect osteoblast precursors or osteoblasts and therefore bone formation [46][47][48][49][50]. If in ammation is localized to the subepithelial space, it is unlikely to induce damage to the underlying bone.…”

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

“…These immune cells, in turn, produce various in ammatory cytokines that are thought to be primarily produced by leukocytes, including IL-1, IL-6, IL-7, IL-17, and TNF-α, which defend against bacterial infection but may indirectly stimulate osteoclastogenesis and bone resorption. Other cytokines, such as CXCL10, CXCL12, CXCL13, and CCL5, may affect osteoblast precursors or osteoblasts and therefore bone formation [48][49][50][51][52]. If in ammation is localized to the subepithelial space, it is unlikely to induce damage to the underlying bone.…”

Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit mandibular bone defect model

“…Bone defect repairing is one of the major challenges in regenerative medicine. Despite the high repair capability, spontaneous restoration of vast bone defects does not perform well for specific conditions such as trauma, fractures, and crushing [ 1 – 3 ]. The gold standard of bone defects treatment is autogenic transplantation, especially from iliac bones [ 4 ]; however, allogeneic and xenogenic grafts have also been used for bone regeneration.…”