Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of jaw-like lesions in mice

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)

Background Definitive treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) have not been developed. Cell-based therapy is an attractive treatment method for intractable diseases in the medical and dental fields; however, approval has been challenging in dentistry. Recently, we developed quality- and quantity (QQ)-controlled peripheral blood mononuclear cells (PBMNCs) that have anti-inflammatory and pro-angiogenesis effects. The aim of this study was to investigate the effects of QQ-controlled PBMNC transplantation on BRONJ-like lesions in mice. Methods To create high-prevalence BRONJ-like lesions, cyclophosphamide (CY) and zoledronate (ZA) were used with tooth extraction. Drug treatment was performed for 5 weeks. QQ-controlled PBMNC transplantation was performed immediately following tooth extraction of both maxillary first molars at 3 weeks after drug administration. Mice were euthanized at 2 weeks post-extraction. Histomorphometric and immunohistochemical analyses, microcomputed tomography assessment, and quantitative polymerase chain reaction evaluation were conducted using maxillae and long bones. Results ZA effects on long bones were noted, regardless of CY. Severely inhibited osseous and soft tissue wound healing of tooth extraction sockets was induced by CY/ZA combination therapy, which was diagnosed as BRONJ-like lesions. QQ-controlled PBMNC

Evidence level

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

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