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

机译:间充质干细胞之间的相互作用治疗下颌骨药物性坏死

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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.
机译:背景已经从包括骨髓,脂肪和粘膜在内的多种组织中分离出间充质干细胞(MSC)。 MSC具有自我更新和分化的能力。关于MSCs的系统管理的报告已经发表,通过植入和分化导致功能改善,从而提供了再生受损组织的新策略。近来,已经清楚的是,MSC具有免疫调节特性,因此可以用于治疗疾病。但是,MSC的治疗作用机制尚未确定。在这里,我们使用与药物相关的颌骨坏死(MRONJ)小鼠模型研究了这些机制。方法为了产生类似MRONJ的特征,小鼠每周两次接受唑来膦酸盐和地塞米松静脉注射。静脉注射后1周,拔出上颌第一磨牙,拔牙后1周,从小鼠股骨和胫骨的骨髓中分离出MSC。为了比较来自MRONJ样小鼠(d-MSC)的“病态MSC”和未经治疗的小鼠(c-MSC)的“对照MSC”,通过分化和集落形成单位成纤维细胞(CFU-F)分析对分离的MSC进行了分析。将d-MSC或c-MSC全身移植到MRONJ样小鼠中。此外,我们观察到在共培养期间,每种MSC类型的所有组合在d-MSC和c-MSC之间细胞含量的交换。结果d-MSC在分化和CFU-F分析中均次于c-MSC。此外,d-MSC治疗组在MRONJ样小鼠中未显示早期愈合。在任意组合的共培养中,MSC对形成细胞间接触并交换细胞内含物。有趣的是,c-MSC和d-MSC之间的交换比其他对更频繁地观察到,并且d-MSC与c-MSC可以区分。结论c-MSCs与d-MSCs的相互作用,包括细胞内物质的交换,有助于d-MSCs的治疗潜力。这种细胞行为可能是MSC用于MRONJ的一种治疗机制。

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