Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw

Abstract Background Mesenchymal 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. Methods To 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. Results d-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. Conclusions The 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.http://deepblue.lib.umich.edu/bitstream/2027.42/134630/1/13287_2016_Article_367.pd

Long Term Retention of Gingival Sealing around Titanium Implants with CaCl2 Hydrothermal Treatment: A Rodent Study

We previously reported that CaCl2 hydrothermal-treated (Ca-HT) titanium (Ti) implants induced a tight sealing at the interface between the implant and peri-implant epithelium (PIE) after implantation. However, it is not clear how long this improved epithelium sealing can be maintained. We subsequently investigated whether the positive effect of Ca-HT to promote sealing between the PIE and implant was sustained longer term. Maxillary molars were extracted from rats and replaced with either Ca-HT implants (Ca-HT group), distilled water-HT implants (DW-HT group) or non-treated implants (control group). After 16 weeks, the majority of implants in the Ca-HT group remained at the maxillary with no apical extension of the PIE. Conversely, half the number of control implants was lost following down-growth of the PIE. The effect of Ca-HT on migration and proliferation of rat oral epithelial cells (OECs) was also investigated. In OECs cultured on Ca-HT Ti plates, protein expression in relation to cell migration decreased, and proliferation was higher than other groups. Surface analysis indicated HT enhanced the formation of surface TiO2 layer without altering surface topography. Consequently, Ca-HT of Ti reduced PIE down-growth via tight epithelial attachment to the surface, which may enhance implant capability for a longer time post-implantation

Long Term Retention of Gingival Sealing around Titanium Implants with CaCl2 Hydrothermal Treatment : A Rodent Study

We previously reported that CaCl2 hydrothermal-treated (Ca-HT) titanium (Ti) implants induced a tight sealing at the interface between the implant and peri-implant epithelium (PIE) after implantation. However, it is not clear how long this improved epithelium sealing can be maintained. We subsequently investigated whether the positive effect of Ca-HT to promote sealing between the PIE and implant was sustained longer term. Maxillary molars were extracted from rats and replaced with either Ca-HT implants (Ca-HT group), distilled water-HT implants (DW-HT group) or non-treated implants (control group). After 16 weeks, the majority of implants in the Ca-HT group remained at the maxillary with no apical extension of the PIE. Conversely, half the number of control implants was lost following down-growth of the PIE. The effect of Ca-HT on migration and proliferation of rat oral epithelial cells (OECs) was also investigated. In OECs cultured on Ca-HT Ti plates, protein expression in relation to cell migration decreased, and proliferation was higher than other groups. Surface analysis indicated HT enhanced the formation of surface TiO2 layer without altering surface topography. Consequently, Ca-HT of Ti reduced PIE down-growth via tight epithelial attachment to the surface, which may enhance implant capability for a longer time post-implantation