Nonirradiated NOD/SCID-human chimeric animal model for primary human multiple myeloma -: A potential in vivo culture system
Nonirradiated NOD/SCID-human chimeric animal model for primary human multiple myeloma -: A potential in vivo culture system
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DOI：
10.1016/s0002-9440(10)63162-8
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发表时间：
2004-02-01
影响因子：
6
通讯作者：
Hsu, SM
中科院分区：
文献类型：
--
作者：
Huang, SY;Tien, HF;Hsu, SM
通过将人胎儿骨（FB）植入NOD/SCID小鼠（NODI SCID-hu（+））的皮下部位，然后将从多发性骨髓瘤（MM）患者获得的原代骨髓单核细胞（BMNC）接种到FB中，产生NOD/SCID人嵌合动物模型。接种30例MM患者的BMNC，其中28例（93%）在NOD/SCID-hu（+）小鼠中显示骨髓瘤细胞（MC）肿瘤生长的证据。有趣的是，28例患者的BMNC中有17例（61%）不仅在FB的骨髓中发生骨髓瘤，而且沿骨膜沿着发生髓外大肿瘤（EMT）。的FB。这些EMT中的肿瘤细胞具有浆细胞样形态，并保留了与亲本MC中相似（如果不相同）的抗原和细胞遗传学。此外，来自9个EMT的小肿瘤块被移植到随后的没有人FB的受体NOD/SCID小鼠（NOD/SCID-hu（-））的皮下部位，除了一个之外，所有的都成功生长。其中两种EMT在动物模型中维持了12个月以上。NOD/SCID-hu（+）嵌合体动物模型对原代MCs的生长有很高的效率，并呈现出人MM的临床特征。移植的MCs可在NOD/SCID-hu（-）小鼠体内培养。
The NOD/SCID human chimeric animal model was generated by implanting of human fetal bones (FBs) into subcutaneous sites of NOD/SCID mice (NODI SCID-hu(+)), followed by inoculation of primary bone marrow mononuclear cells (BMNCs) obtained from patients with multiple myeloma (MM) into the FBs. The BMNCs from 30 patients with MM were inoculated, and 28 (93%) of them revealed evidence of tumor growth of myeloma cells (MCs) in the NOD/SCID-hu(+) mice. Intriguingly, 17 (61%) of the 28 patients' BMNCs inoculated developed not only myeloma in the bone marrow of the FBs, but also extramedullary macrotumors (EMTs) along the periosteum. of the FBs. The tumor cells in these EMTs had plasmacytoid morphology and preserved antigens and cytogenetics similar, if not identical, to those in the parent MCs. Moreover, small tumor blocks from nine EMTs were transplanted into subcutaneous sites of subsequent recipient NOD/SCID mice without human FBs (NOD/SCID-hu(-)), and all but one grew successfully. Two of the EMTs have been maintained in the animal model for more than 12 months. The NOD/SCID-hu(+) chimeric animal model is highly efficient for growth of primary MCs and presents clinical features of human MM. The engrafted MCs can be maintained dsubsequently in NOD/SCID-hu(-) mice as in vivo culture..