Introduction: Stem cells have great therapeutic potential due to their capacity for self-renewal and their potential\nfor differentiating into multiple cell lineages. It has been recently shown that the host immune system has\nfundamental effects on the fate of transplanted mesenchymal stem cells during bone repair, where the topical\nadministration of aspirin is capable of improving calvarial bone repair in rodents by inhibiting tumor necrosis factor-Ã?±\n(TNF-Ã?±) and interferon-Ã?³ (IFN-Ã?³) production. This study investigates whether aspirin is capable of accelerating the\nregenerative potential of bone marrow mesenchymal stem cells (BMSC) in a mini swine calvarial bone defect model.\nMethods: Calvarial bone defects (3 cm Ã?â?? 1.8 cm oval defect) in mini swine were treated with BMSC pretreated\nwith 75 Ã?¼g/ml aspirin for 24 h seeded onto hydroxyaptite/tricalcium phosphatel (HA/TCP), or with BMSC with\nHA/TCP, or with HA/TCP only, or remained untreated. Animals were scanned with micro-computed tomography\n(microCT) at 2 days and 6 months postsurgery and were sacrificed at 6 months postsurgery with decalcified\ntissues being processed for histomorphometric examination. The cytokine levels, including TNF-Ã?± and IFN-Ã?³, were\nmeasured by enzyme-linked immunosorbent assay (ELISA).\nResults: Aspirin at 75 Ã?¼g/ml promoted the osteogenesis of BMSC in vitro and in vivo, shown by Alizarin Red staining\nand new bone volume in the nude mice transplantation model (p < 0.01), respectively. Defects treated with\naspirin-BMSC showed significantly greater new bone fill compared with other three groups at 6 months post surgery\n(p < 0.01). Aspirin-BMSC treatment has significantly decreased the concentration of TNF-Ã?± and IFN-Ã?³ (p < 0.05).\nConclusions: The present study shows that BMSC pretreated with aspirin have a greater capacity to repair calvarial\nbone defects in a mini swine model. The results suggest that the administration of aspirin is capable of improving\nBMSC-mediated calvarial bone regeneration in a big animal model.
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