Paton-Hough J, Chantry A D, Lawson M A
Sheffield Myeloma Research Team, Department of Oncology, The University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Bone. 2015 Aug;77:57-68. doi: 10.1016/j.bone.2015.04.004. Epub 2015 Apr 11.
Pre-clinical in vivo models of multiple myeloma are essential tools for investigating the pathophysiology of multiple myeloma and for testing new therapeutic agents and strategies prior to their potential use in clinical trials. Over the last five decades, several different types of murine models of multiple myeloma have been developed ranging from immunocompetent syngeneic models, e.g. the 5 T series of myeloma cells, to immunocompromised models including the SCID xenograft models, which use human myeloma cell lines or patient-derived cells. Other models include hybrid models featuring the implantation of SCID mice with bone chips (SCID-hu or SCID-rab) or 3-D bone scaffolds (SCID-synth-hu), and mice that have been genetically engineered to develop myeloma. Bearing in mind the differences in these models, it is not surprising that they reflect to varying degrees different aspects of myeloma. Here we review the past and present murine models of myeloma, with particular emphasis on their advantages and limitations, characteristics, and their use in testing therapeutic agents to treat myeloma tumour burden and bone disease.
多发性骨髓瘤的临床前体内模型是研究多发性骨髓瘤病理生理学以及在潜在用于临床试验之前测试新治疗药物和策略的重要工具。在过去的五十年中,已经开发了几种不同类型的多发性骨髓瘤小鼠模型,从免疫健全的同基因模型,例如5T系列骨髓瘤细胞,到免疫缺陷模型,包括使用人骨髓瘤细胞系或患者来源细胞的SCID异种移植模型。其他模型包括将SCID小鼠植入骨芯片(SCID-hu或SCID-rab)或3-D骨支架(SCID-synth-hu)的杂交模型,以及经过基因工程改造以发展骨髓瘤的小鼠。考虑到这些模型的差异,它们在不同程度上反映骨髓瘤的不同方面也就不足为奇了。在这里,我们回顾骨髓瘤的过去和现在的小鼠模型,特别强调它们的优点和局限性、特征,以及它们在测试治疗药物以治疗骨髓瘤肿瘤负荷和骨疾病方面的用途。