三种人多发性骨髓瘤细胞系移植小鼠模型的建立和比较

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.