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Application of mesenchymal stromal cell sheets to prevent medication-related osteonecrosis of the jaw with titanium implants in rats

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Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable adverse event. Dental implants are one of the triggering factors of MRONJ, and implant therapy with low MRONJ risk is required. This study aimed to investigate a rat model of MRONJ induced by extraoral placement of titanium materials and the use of mesenchymal stromal cell (MSCs) sheets to prevent MRONJ. Eight-week-old male rats were administered zoledronate and dexamethasone thrice weekly until killing. A week after drug initiation, a titanium screw and a plate were placed on the left buccal side of the mandible. Allogeneic bone marrow-derived MSC sheets were co-grafted with the titanium plates in the MSC sheet ( +) group. Six weeks after titanium placement, the rats were killed, and their excised mandibular bones were subjected to micro-computed tomography (CT) analysis. Histological analysis was performed after the titanium implants were removed. Empty lacunae visualized on hematoxylin and eosin staining were used as evidence of bone necrosis. Bone necrosis was reduced in the MSC sheet ( +) group. Tartrate-resistant acid phosphatase (TRAP) staining revealed a decreased number of TRAP-positive cells in areas with a large number of empty lacunae in the MSC sheet (–) group. Micro-CT analyses demonstrated that the bone volume fraction (BV/TV) was not significantly different between the MSC sheet (–) and ( +) groups. We conclude that MRONJ can be triggered by a titanium placement in rats, and grafting of allogeneic MSC sheets has the potential to prevent MRONJ.

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The data of this study are available from the corresponding author on reasonable request.

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Acknowledgements

We are indebted to Professor D. W. Grainger of the University of Utah, USA, for providing a technical review of this study. This work was partially supported by the Japan Society for the Promotion of Science (Grant Numbers 20K18681, 23K09362, and 18K09623). 

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Authors and Affiliations

  1. Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Kazuhiro Nishimaki, Nobuyuki Kaibuchi, Kaoru Washio & Masayuki Yamato

  2. Department of Oral and Maxillofacial Surgery, Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Nobuyuki Kaibuchi

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  1. Kazuhiro Nishimaki
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Correspondence to Nobuyuki Kaibuchi.

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All animal experimental protocols used in this study were approved by the Animal Welfare Committee of Tokyo Women’s Medical University (agreement number AE21-021) and conducted according to all applicable institutional and/or national guidelines for the care and use of animals.

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Nishimaki, K., Kaibuchi, N., Washio, K. et al. Application of mesenchymal stromal cell sheets to prevent medication-related osteonecrosis of the jaw with titanium implants in rats. Odontology (2024). https://doi.org/10.1007/s10266-024-00900-w

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