Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.
目的： 利用人骨髓瘤细胞系ARP1、MM.1S和NCI-H929建立异种移植模型，并对三种细胞移植后生长周期、肿瘤负荷和生物学特点进行比较。 方法： 将ARP1、MM.1S和NCI-H929细胞分别由皮下或尾静脉植入经(137)Cs照射后的NOD/SCID小鼠，每周观察小鼠的生存情况，监测肿瘤负荷。应用流式细胞术检测小鼠肿瘤组织或骨髓中CD138(+)细胞的比例。采用免疫荧光检测肿瘤组织细胞的CD138和免疫球蛋白轻链表达。ELISA法检测骨髓和外周血中的免疫球蛋白轻链，micro-CT评价骨病变。 结果： 皮下移植ARP1、MM.1S和NCI-H929细胞的小鼠在两周内均可形成局部肿瘤，免疫荧光检测支持浆细胞肿瘤。尾静脉移植后第20天时可在ARP1组小鼠外周血中检测出κ轻链[（8.2±1.0）ng/ml]。尾静脉移植6周左右，ARP1组小鼠出现体重下降、精神萎靡、下肢逐渐瘫痪等表现，骨髓中能检测到人CD138(+)CD38(+)细胞群，予硼替佐米治疗可显著降低肿瘤负荷[（5.7±0.2）%对（21.3±2.1）%，P<0.01]。MM.1S和NCI-H929组小鼠骨髓中未检测到人CD138(+)CD38(+)细胞群。 结论： ARP1、MM.1S和NCI-H929细胞系构建的小鼠模型可作为MM发病机制及临床研究的良好模型。.
Keywords: Mice; Models; Multiple myeloma.