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[三种人多发性骨髓瘤细胞系小鼠移植模型的建立与比较]

[Establishment and comparison of three human multiple myeloma cell line transplantation models in mice].

作者信息

Liu L T, Wei X J, Gong L X, Yu Z, Qiu L G, Hao M

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2022 May 14;43(5):414-419. doi: 10.3760/cma.j.issn.0253-2727.2022.05.011.

Abstract

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. 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. 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) %, <0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. 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.

摘要

利用人骨髓瘤细胞系ARP1、MM.1S和NCI-H929建立三种异种移植模型,并比较移植后三种细胞的增殖、肿瘤负荷及生物学特性。将人骨髓瘤细胞系ARP1、MM.1S和NCI-H929的悬液通过皮下注射或尾静脉注射接种到NOD/SCID小鼠体内。每周观察小鼠存活情况并测量肿瘤负荷。采用流式细胞术检测肿瘤组织或小鼠骨髓中CD138(+)细胞的比例。通过免疫荧光检测CD138(+)细胞和轻链。采用ELISA法检测骨髓和外周血中的轻链,并通过显微CT评估骨病情况。注射ARP1、MM.1S和NCI-H929细胞的小鼠均在约2周内在皮下形成肿瘤。免疫荧光检测支持浆细胞瘤。尾静脉移植后第20天,ARP1小鼠外周血中检测到κ轻链(8.2±1.0 ng/ml)。尾静脉移植6周后,ARP1组小鼠出现体重减轻、精神抑郁和拖腿症状,骨髓中检测到人类CD138(+)CD38(+)细胞。此外,肿瘤形成后给予硼替佐米(BTZ)治疗可显著降低肿瘤负荷[(5.7±0.2)%对(21.3±2.1)%,<0.01]。MM.1S或NCI-H929组的骨髓中未检测到人类CD138(+)CD38(+)细胞。本研究结果表明,由三种细胞系(ARP1、MM.1S和NCI-H929)构建的小鼠模型可作为多发性骨髓瘤发病机制和临床研究的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69c4/9250955/fe279be08859/cjh-43-05-414-g001.jpg

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