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

Kenichi Ogata, Masashi Osugi, Takamasa Kawai, Yukiko Wakayama, Kohei Sakaguchi, Seiji Nakamura, Wataru Katagiri

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)445-451
Number of pages7
JournalJournal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Issue number5
Publication statusPublished - Sept 2018

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oral Surgery
  • Pathology and Forensic Medicine
  • Otorhinolaryngology


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