Secretomes of mesenchymal stem cells induce early bone regeneration by accelerating migration of stem cells

Objective: We previously reported that secretomes from human bone marrow-derived mesenchymal stem cells (MSC-CM) have a strong potential to accelerate bone regeneration. The most important initial step for bone regeneration is osteoprogenitor cell migration to bone defects. We hypothesized that MSC-CM enhance the migration of endogenous stem cells earlier to the local lesioned part. In this study, we investigated the potential of MSC-CM to induce in vivo early bone regeneration by accelerating cell migration in a rat calvarial bone defect model. Materials and methods: Cytokine array analysis was performed to assess the types of cytokines included in MSC-CM. Bone defects (5 mm in diameter) were created in the calvarial bones of rats, and the damaged areas were implanted with atelocollagen suspended in MSC-CM or phosphate buffered saline. After 2 and 4 weeks, radiographic and histological analyses were performed. Furthermore, rat mesenchymal stem cells (rMSCs) were labeled with the lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR), and the rats were photographed at various times after injection of the DiR-labeled rMSCs using in vivo imaging. Results: MSC-CM contained many factors with respect to cell migration and tissue regeneration. Bone regeneration in rat calvaria was observed earliest in the MSC-CM implantation group. Migration of the labeled rMSCs from the tail toward the calvaria, where MSC-CM was implanted, was observed during the first 24 h after injection in the MSC-CM implantation group using in vivo imaging. Immunohistochemistry also indicated early cell migration. Conclusion: MSC-CM enhanced the migration of endogenous stem cells facilitating earlier bone regeneration.