Allogeneic multipotent mesenchymal stromal cell sheet transplantation promotes healthy healing of wounds caused by zoledronate and dexamethasone in canine mandibular bones

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Many cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is an intractable disease, have been reported. Although a general intravenous injection of multipotent mesenchymal stromal cells (MSCs) may be effective for treating BRONJ, it has some severe problems. Therefore, our aim was to develop a treatment of locally administered MSCs. In this study, we investigated the effect of MSC sheet transplantation in the mandibular bone healing in beagle dogs, which were administered zoledronate and dexamethasone. Methods MSCs isolated from subcutaneous fat were seeded onto temperature-responsive culture dishes to produce MSC sheets. Zoledronate and dexamethasone were administered to beagle dogs. Then, the parts of mandibular cortical bones were removed, and MSC sheets were transplanted to cover those bone defects (MSC sheet transplant side) or not (Control side). The specimens were evaluated in micro CT, histology, and immunohistochemistry. Results Four weeks after surgery, redness and swellings were observed in the mucosal wounds of the control sides of 2 of 3 dogs. In contrast, the mucosal wounds of the MSC sheet transplant sides of all dogs completely healed. Histological images showed some free sequestrums and many bacterial colonies, and Immunohistological analysis showed some cathepsin K-positive multinuclear cells detached from jaw bone surfaces in

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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