Abstract
BackgroundMesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa. MSCs have the capacity for self-renewal and differentiation. Reports have been published on the systemic administration of MSCs leading to functional improvements by engraftment and differentiation, thus providing a new strategy to regenerate damaged tissues. Recently, it has become clear that MSCs possess immunomodulatory properties and can therefore be used to treat diseases. However, the therapeutic effect mechanisms of MSCs are yet to be determined. Here, we investigated these mechanisms using a medication-related osteonecrosis of the jaw (MRONJ)-like mouse model.MethodsTo generate MRONJ-like characteristics, mice received intravenous zoledronate and dexamethasone two times a week. At 1 week after intravenous injection, maxillary first molars were extracted, and at 1 week after tooth extraction, MSCs were isolated from the bone marrow of the mice femurs and tibias. To compare “diseased MSCs” from MRONJ-like mice (d-MSCs) with “control MSCs” from untreated mice (c-MSCs), the isolated MSCs were analyzed by differentiation and colony-forming unit-fibroblast (CFU-F) assays and systemic transplantation of either d-MSCs or c-MSCs into MRONJ-like mice. Furthermore, we observed the exchange of cell contents among d-MSCs and c-MSCs during coculture with all combinations of each MSC type.Resultsd-MSCs were inferior to c-MSCs in differentiation and CFU-F assays. Moreover, the d-MSC-treated group did not show earlier healing in MRONJ-like mice. In cocultures with any combination, MSC pairs formed cell–cell contacts and exchanged cell contents. Interestingly, the exchange among c-MSCs and d-MSCs was more frequently observed than other pairs, and d-MSCs were distinguishable from c-MSCs.ConclusionsThe interaction of c-MSCs and d-MSCs, including exchange of cell contents, contributes to the treatment potential of d-MSCs. This cellular behavior might be one therapeutic mechanism used by MSCs for MRONJ.
Highlights
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa
medicationrelated osteonecrosis of the jaw (MRONJ)-like mouse model Figure 1a details the experimental schedules and methods of our study. diseased MSCs” from MRONJ-like mice (d-MSCs) were isolated from the bone marrow obtained from the femurs and tibias of wild-type C57BL/6 N mice, which received both Dex and Zol administered intravenously for 2 weeks
Characteristics of d-MSCs d-MSCs from MRONJ mice had a higher proliferation rate compared with control mesenchymal stem cell (c-MSC) from normal mice, as estimated by EdU exposure and colony-forming unit-fibroblast (CFU-F) (Fig. 1b)
Summary
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa. The therapeutic effect mechanisms of MSCs are yet to be determined We investigated these mechanisms using a medicationrelated osteonecrosis of the jaw (MRONJ)-like mouse model. Medication-related osteonecrosis of the jaw (MRONJ) is defined as exposed necrotic bone in the oral cavity that displays intractable symptoms which cannot be cured for more than 8 weeks, and has never received radiation treatment [1]. This condition appears to be nearly synonymous with bisphosphonate-related osteonecrosis of the jaw (BRONJ) [2]. Because the etiology of MRONJ is not clear the fundamental method of clinical treatment for this disease is not recognized, and novel treatments are required for immediate worldwide application
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
