Abstract
Host blood circulating stem cells are an important cell source that participates in the repair of damaged tissues. The clinical challenge is how to improve the recruitment of circulating stem cells into the local wound area and enhance tissue regeneration. Stromal-derived factor-1 (SDF-1) has been shown to be a potent chemoattractant of blood circulating stem cells into the local wound microenvironment. In order to investigate effects of SDF-1 on bone development and the repair of a large bone defect beyond host self-repair capacity, the BMP-induced subcutaneous ectopic bone formation and calvarial critical-sized defect murine models were used in this preclinical study. A dose escalation of SDF-1 were loaded into collagen scaffolds containing BMP, VEGF, or PDGF, and implanted into subcutaneous sites at mouse dorsa or calvarial critical-sized bone defects for 2 and 4 weeks. The harvested biopsies were examined by microCT and histology. The results demonstrated that while SDF-1 had no effect in the ectopic bone model in promoting de novo osteogenesis, however, in the orthotopic bone model of the critical-sized defects, SDF-1 enhanced calvarial critical-sized bone defect healing similar to VEGF, and PDGF. These results suggest that SDF-1 plays a role in the repair of large critical-sized defect where more cells are needed while not impacting de novo bone formation, which may be associated with the functions of SDF-1 on circulating stem cell recruitment and angiogenesis.
Highlights
Cells are critical to the success of tissue engineering
Cartilage still existed at 4 weeks, more intermediate type of cartilage-bone transition was observed remaining at BMP groups containing high doses of Stromal-derived factor-1 (SDF-1)(10 mg and 3 mg)
We investigated SDF-1 effects on bone formation both ectopically and in critical-sized bone defects
Summary
Cells are critical to the success of tissue engineering. Any tissue repair and regeneration depends on its tissue-specific differentiated cells to produce its own extracellular matrix. There have been two types of cells used for cell therapy: differentiated/mature cells and undifferentiated/stem cells. Ex vivo stem cell therapy encounters major challenges on excessive costs for in vitro cell manipulation [1,2], risks for contaminations, pathogen transmission [3], and tumorigenesis [2,4]. To overcome these shortcomings, application of chemokines to promote ‘‘homing’’ of host circulating stem cells to a wound may provide a potential to increase the number of local stem cells and improve tissue regeneration
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