Transplantation of Noncultured Stromal Vascular Fraction Cells of Adipose Tissue Ameliorates Osteonecrosis of the Jaw-Like Lesions in Mice
Transplantation of Noncultured Stromal Vascular Fraction Cells of Adipose Tissue Ameliorates Osteonecrosis of the Jaw-Like Lesions in Mice
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DOI：
10.1002/jbmr.3292
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发表时间：
2018-01-01
影响因子：
6.2
通讯作者：
Sawase, Takashi
中科院分区：
文献类型：
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作者：
Kuroshima, Shinichiro;Sasaki, Muneteru;Sawase, Takashi
双膦酸盐相关性颌骨骨坏死（BRONJ）的确切病因和有效治疗策略尚不清楚。非培养基质血管部分（SVF）细胞移植已被证明是替代干细胞治疗的一种有用的再生医学方法。本研究探讨非培养SVF移植对小鼠拔牙窝愈合的影响。雌性C57BL/6J小鼠化疗/双膦酸盐联合治疗7周，给药后3周拔除上颌第一磨牙。拔牙后4周，采用大体伤口愈合和组织形态测量法验证骨和软组织伤口愈合情况。在这里，我们创建了一个模拟人类进展的高患病率ONJ样病变的新动物模型，因为人类ONJ主要发生在拔牙后接受化疗和双膦酸盐治疗的女性患者中。此外，化疗和双膦酸盐联合治疗5周的小鼠在给药后3周拔牙后接受SVF移植。拔牙后2周实施安乐死，通过大体伤口愈合、组织形态学、免疫组织形态学、定量实时聚合酶链反应和显微计算机断层扫描来评估移植对伤口愈合的影响。我们发现非培养SVF细胞的全身移植通过改善拔牙槽骨和软组织的愈合来改善onj样病变。SVF治疗明显增加血管和M2/M1巨噬细胞的比例。此外，SVF移植减少了来自骨表面的抗酒石酸酸性磷酸酶阳性（TRAP(+)）单核细胞（MNCs）和非附着性破骨细胞的增加，这些细胞在化疗/双膦酸盐联合治疗的拔牙槽和骨髓结缔组织中被显著检测到。我们的研究结果表明，非培养的SVF细胞移植是治疗BRONJ的合适方法。系统性和局部环境中异常的TRAP(+) MNCs和非附着性破骨细胞可能促进BRONJ的发展。(c) 2017年美国骨与矿物研究学会。
The precise pathoetiology and effective treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) remain unknown. Transplantation of noncultured stromal vascular fraction (SVF) cells has been shown to be a useful method for regenerative medicine in place of stem cell therapy. This study investigated the effects of noncultured SVF transplantation on tooth extraction socket healing in mice. Both chemotherapeutic/bisphosphonate combination therapy for 7 weeks and tooth extraction of maxillary first molars at 3 weeks after drug administration were performed using female C57BL/6J mice. Osseous and soft tissue wound healing were validated at 4 weeks postextraction using gross wound healing and histomorphometry. Here, we created a new animal model of high-prevalence ONJ-like lesions that mimic human progression, because human ONJ mainly occurs in female patients taking both chemotherapeutic and bisphosphonate following tooth extraction. Moreover, mice with chemotherapeutic and bisphosphonate combination therapy for 5 weeks received SVF transplantation just after tooth extraction at 3 weeks post-drug administration. Euthanasia was performed at 2 weeks postextraction to assess the transplantation effects on wound healing using gross wound healing, histomorphometry, immunohistomorphometry, quantitative real-time polymerase chain reaction, and microcomputed tomography. We showed that systemic transplantation of noncultured SVF cells ameliorates ONJ-like lesions by improving both osseous and soft tissue healing of tooth extraction sockets. SVF therapy significantly increased blood vessels and the ratio of M2/M1 macrophages. In addition, SVF transplantation reduced the increases in tartrate-resistant acid phosphatase-positive (TRAP(+)) mononuclear cells (MNCs) and nonattached osteoclasts from the bone surface, which were significantly detected in the connective tissue of tooth extraction sockets and bone marrow by chemotherapeutic/bisphosphonate combination therapy. Our findings suggest that transplantation of noncultured SVF cells is a suitable treatment for BRONJ. Abnormal TRAP(+) MNCs and nonattached osteoclasts in systemic and local environments may contribute to the development of BRONJ. (c) 2017 American Society for Bone and Mineral Research.