Penn Image-Guided Interventions Laboratory, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA, 19104, USA.
Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA, 19104, USA.
Sci Rep. 2019 Jul 22;9(1):10546. doi: 10.1038/s41598-019-47104-9.
While patient-derived xenograft (PDX) models of hepatocellular carcinoma (HCC) have been successfully generated from resected tissues, no reliable methods have been reported for the generation of PDXs from patients who are not candidates for resection and represent the vast majority of patients with HCC. Here we compare two methods for the creation of PDXs from HCC biopsies and find that implantation of whole biopsy samples without the addition of basement membrane matrix favors the formation of PDX tumors that resemble Epstein-Barr virus (EBV)-driven B-cell lymphomas rather than HCC tumors. In contrast, implantation with Matrigel supports growth of HCC cells and leads to a high rate of HCC tumor formation from these biopsies. We validate the resulting PDXs, confirm their fidelity to the patients' disease and conclude that minimally invasive percutaneous liver biopsies can be used with relatively high efficiency to generate PDXs of HCC.
虽然已经成功地从切除的组织中生成了肝癌 (HCC) 的患者来源异种移植 (PDX) 模型,但对于不能进行切除且代表大多数 HCC 患者的患者,尚无可靠的方法来生成 PDX。在这里,我们比较了两种从 HCC 活检中创建 PDX 的方法,发现不添加基底膜基质而植入整个活检样本有利于形成 PDX 肿瘤,这些肿瘤类似于 Epstein-Barr 病毒 (EBV) 驱动的 B 细胞淋巴瘤,而不是 HCC 肿瘤。相比之下,植入 Matrigel 支持 HCC 细胞的生长,并导致从这些活检中形成 HCC 肿瘤的高比率。我们验证了得到的 PDX,确认它们与患者疾病的一致性,并得出结论,微创经皮肝活检可以相对高效地用于生成 HCC 的 PDX。