Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw.
Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw.
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DOI：
10.1186/s13287-016-0367-3
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发表时间：
2016-08-17
影响因子：
7.5
通讯作者：
Koyano K
中科院分区：
文献类型：
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作者：
Matsuura Y;Atsuta I;Ayukawa Y;Yamaza T;Kondo R;Takahashi A;Ueda N;Oshiro W;Tsukiyama Y;Koyano K
间充质干细胞（MSC）已从多种组织中分离，包括骨髓、脂肪和粘膜。MSC具有自我更新和分化的能力。已经发表了关于全身施用MSC的报告，其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。最近，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。然而，MSC的治疗作用机制尚未确定。在这里，我们研究了这些机制，使用药物相关的颌骨骨坏死（MRONJ）样小鼠模型。为了产生MRONJ样特征，小鼠每周两次静脉注射唑来膦酸盐和地塞米松。静脉注射后1周，拔除上颌第一磨牙，拔牙后1周，从小鼠股骨和胫骨的骨髓中分离MSC。为了比较来自MRONJ样小鼠（d-MSC）的“患病MSC”与来自未处理小鼠（c-MSC）的“对照MSC”，通过分化和集落形成单位成纤维细胞（CFU-F）测定以及将d-MSC或c-MSC全身移植到MRONJ样小鼠中来分析分离的MSC。此外，我们观察到在与每种MSC类型的所有组合共培养期间，d-MSC和c-MSC之间的细胞内容物的交换。在分化和CFU-F测定中，d-MSCs劣于c-MSCs。此外，d-MSC治疗组在MRONJ样小鼠中没有显示出更早的愈合。在任何组合的共培养中，MSC对形成细胞-细胞接触并交换细胞内容物。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是可区分的。c-MSC和d-MSC的相互作用，包括细胞内容物的交换，有助于d-MSC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。
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. 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. 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. 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.