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将来自骨巨细胞瘤患者的肿瘤细胞经胫骨内注射到裸鼠体内会引发溶骨反应。

Intratibial injection of patient-derived tumor cells from giant cell tumor of bone elicits osteolytic reaction in nude mouse.

作者信息

Xu Leqin, Wu Zhipeng, Zhou Zhenhua, Yang Xinghai, Xiao Jianru

机构信息

Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.

Department of Science and Education, Xiamen Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Xiamen, Fujian 361001, P.R. China.

出版信息

Oncol Lett. 2018 Oct;16(4):4649-4655. doi: 10.3892/ol.2018.9148. Epub 2018 Jul 16.

Abstract

There have been various reports in the literature of an model for giant cell tumor of bone (GCTB). However, few suitable animal models of GCTB have been established, due to the fact that GCTB contains three histologically different cell types. To the best of our knowledge, injection of patient-derived GCTB cells into bone environment has not been reported until now. In the present study, the biological behavior of GCTB cells in nude mice was investigated through intratibial injection of patient-derived GCTB cells. Patient-derived GCTB cells were obtained from 5 patients who had not undergone chemo- and radiotherapy. Once isolated, the cell suspension was injected into the tibias of nude mice. The growth process was monitored by weekly observation and photographic documentation using X-ray. Four months after injection, nude mice were sacrificed and the injected tibial samples were fixed, and further analyzed using micro-computed tomography (micro-CT), standard histology, tartrate-resistant acid phosphatase (TRAP) staining and mitochondrial immunofluorescence staining. X-ray, micro-CT and standard histology revealed osteolytic destruction in the proximal end of the tibia. TRAP staining identified TRAP-positive, osteoclast-like cells distributed in the bone marrow interface of the lesion area. Anti-human mitochondrial immunofluorescence staining confirmed that the surviving cells in the osteolytic destruction were of human GCTB cell origin. These findings indicate that intratibial injection of patient-derived GCTB cells may elicit osteolytic destruction in nude mice. The results of the current study present a novel animal model for GCTB, opening new perspectives to investigate this disease and develop therapeutic agents.

摘要

文献中已有关于骨巨细胞瘤(GCTB)模型的各种报道。然而,由于GCTB包含三种组织学上不同的细胞类型,很少有合适的GCTB动物模型被建立。据我们所知,将患者来源的GCTB细胞注射到骨环境中至今尚未见报道。在本研究中,通过向裸鼠胫骨内注射患者来源的GCTB细胞,研究了GCTB细胞在裸鼠体内的生物学行为。患者来源的GCTB细胞取自5例未接受过化疗和放疗的患者。细胞分离后,将细胞悬液注射到裸鼠的胫骨中。通过每周观察并用X射线进行摄影记录来监测生长过程。注射四个月后,处死裸鼠,将注射的胫骨样本固定,并使用微计算机断层扫描(micro-CT)、标准组织学、抗酒石酸酸性磷酸酶(TRAP)染色和线粒体免疫荧光染色进行进一步分析。X射线、micro-CT和标准组织学显示胫骨近端有溶骨性破坏。TRAP染色鉴定出TRAP阳性的破骨细胞样细胞分布在病变区域的骨髓界面。抗人线粒体免疫荧光染色证实溶骨性破坏中存活的细胞来源于人GCTB细胞。这些发现表明,向裸鼠胫骨内注射患者来源的GCTB细胞可能引发裸鼠的溶骨性破坏。本研究结果提出了一种新的GCTB动物模型,为研究该疾病和开发治疗药物开辟了新的视角。

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