Abstract
IntroductionStem cells have great therapeutic potential due to their capacity for self-renewal and their potential for differentiating into multiple cell lineages. It has been recently shown that the host immune system has fundamental effects on the fate of transplanted mesenchymal stem cells during bone repair, where the topical administration of aspirin is capable of improving calvarial bone repair in rodents by inhibiting tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production. This study investigates whether aspirin is capable of accelerating the regenerative potential of bone marrow mesenchymal stem cells (BMSC) in a mini swine calvarial bone defect model.MethodsCalvarial bone defects (3 cm × 1.8 cm oval defect) in mini swine were treated with BMSC pretreated with 75 μg/ml aspirin for 24 h seeded onto hydroxyaptite/tricalcium phosphatel (HA/TCP), or with BMSC with HA/TCP, or with HA/TCP only, or remained untreated. Animals were scanned with micro-computed tomography (microCT) at 2 days and 6 months postsurgery and were sacrificed at 6 months postsurgery with decalcified tissues being processed for histomorphometric examination. The cytokine levels, including TNF-α and IFN-γ, were measured by enzyme-linked immunosorbent assay (ELISA).ResultsAspirin at 75 μg/ml promoted the osteogenesis of BMSC in vitro and in vivo, shown by Alizarin Red staining and new bone volume in the nude mice transplantation model (p < 0.01), respectively. Defects treated with aspirin-BMSC showed significantly greater new bone fill compared with other three groups at 6 months postsurgery (p < 0.01). Aspirin-BMSC treatment has significantly decreased the concentration of TNF-α and IFN-γ (p < 0.05).ConclusionsThe present study shows that BMSC pretreated with aspirin have a greater capacity to repair calvarial bone defects in a mini swine model. The results suggest that the administration of aspirin is capable of improving BMSC-mediated calvarial bone regeneration in a big animal model.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0200-4) contains supplementary material, which is available to authorized users.
Highlights
Stem cells have great therapeutic potential due to their capacity for self-renewal and their potential for differentiating into multiple cell lineages
Aspirin has no effect on the immunophenotype of swine bone marrow mesenchymal stem cells (BMSC) To examine whether aspirin treatment affects the cell surface marker profile of BMSC, cells were treated with 75 μg/ml aspirin for 24 h before their immunophenotype was investigated using flow cytometry
The effect of aspirin on BMSC proliferation BMSC were treated with aspirin at various concentrations (50, 75, 100, and 150 μg/ml) before the rate of cell proliferation was examined with the MTT assay
Summary
Stem cells have great therapeutic potential due to their capacity for self-renewal and their potential for differentiating into multiple cell lineages. It has been recently shown that the host immune system has fundamental effects on the fate of transplanted mesenchymal stem cells during bone repair, where the topical administration of aspirin is capable of improving calvarial bone repair in rodents by inhibiting tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production. We have recently shown that the host immune system has fundamental effects on the fate of transplanted MSC during bone remodeling, where TNF-α and IFN-γ produced by proinflammatory T cells play a critical role [13,14,15]. The topical administration of aspirin, alternatively the systemic infusion of regulatory T cells, is capable of inhibiting TNF-α and IFN-γ production and, improve calvarial bone repair in rodents [13]. The use of aspirin at the sites of tissue damage is less technically challenging than the systemic infusion of regulatory T cells and, can be accepted by clinical practitioners and patients
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