Different effects of cell transplantation on murine MRONJ-like lesions in a cell source-dependent manner

Medication-related osteonecrosis of the jaw (MRONJ) is one of the potential intractable diseases that has no clear pathophysiology and definitive treatment/prevention strategy. Previously, transplantation of quality- and quantity-controlled peripheral blood mononuclear cells (QQ-PBMNCs) or stromal vascular fraction cells (SVFCs) has been demonstrated to reduce/prevent MRONJ-like lesions in mice. However, because the two cell sources were evaluated in separate studies, differences in their effects on osseous and soft tissue healing could not be determined. This study aimed to compare the effects of QQ-PBMNC and SVFC transplantation on osseous and soft tissue healing after normalization to the corresponding control values in a murine model of MRONJ-like lesions. MRONJ-like lesions were created in combination with drug administration (zoledronate and cyclophosphamide) and tooth extraction of both maxillary first molars in female C57BL6/J mice. Prepared QQ-PBMNCs or SVFCs were systemically transplanted following tooth extraction 3 weeks after the start of drug administration. Euthanasia was carried out 2 weeks after tooth extraction. Wound healing-related parameters were compared between MRONJ-like lesions with and without cell-based therapy. The relative superiority of two cell types was evaluated for each parameter. Both cell populations significantly improved osseous and soft tissue healing of tooth extractions in MRONJ-like lesions. Interestingly, SVFCs had superior transplantation effects on osseous healing, and QQ-PBMNCs had superior effects on soft tissue healing of extraction sockets. Transplantation effects were cell source-dependent, with SVFCs and QQ-PBMNCs showing superior efficacy in promoting osseous healing and soft tissue healing, respectively. The selection of optimal cell source may depend on the predominant clinical features of the lesions.