Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation.
Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation.
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DOI：
10.1038/s41598-021-87228-5
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发表时间：
2021-04-07
影响因子：
4.6
通讯作者：
Allen IC
中科院分区：
文献类型：
--
作者：
Hendricks-Wenger A;Aycock KN;Nagai-Singer MA;Coutermarsh-Ott S;Lorenzo MF;Gannon J;Uh K;Farrell K;Beitel-White N;Brock RM;Simon A;Morrison HA;Tuohy J;Clark-Deener S;Vlaisavljevich E;Davalos RV;Lee K;Allen IC
迫切需要治疗胰腺癌的新疗法。然而，有效的干预措施缺乏一个强大的临床前模型，可以概括患者的解剖和生理。同样，用于离体研究的人原发性恶性组织的可用性有限。这些是生物医学设备领域中的显著限制。我们已经使用CRISPR/Cas9开发了RAG 2/IL 2 RG缺陷型猪作为大型动物模型，其具有人胰腺癌的癌症异种移植研究的新应用。在这项概念验证研究中，这些猪是在胚胎中使用按需遗传修饰成功产生的，避免了育种和饲养的需要。将人Panc 01细胞皮下注射到RAG 2/IL 2 RG缺陷型猪的耳中，显示出100%的植入，生长速率与通常在小鼠模型中观察到的生长速率相似。组织学显示无免疫细胞浸润，肿瘤形态与小鼠模型高度一致。发现肿瘤组织的电特性和对不可逆电穿孔的响应与切除的人胰腺癌肿瘤相似。产生的大量肿瘤组织能够提高肿瘤组织电特性的准确性和建模。总之，这表明该模型将是有用的，并且能够弥合将疗法从实验室转化为临床应用的差距。
New therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients’ anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.
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影响因子：
2.8
作者：
Garcia, P. A.;Pancotto, T.;Davalos, R. V.
通讯作者：
Davalos, R. V.
影响因子：
--
作者：
Choi YJ;Kim E;Reza AMMT;Hong K;Song H;Park C;Cho SK;Lee K;Prather RS;Kim JH
通讯作者：
Kim JH
影响因子：
10.6
作者：
He, Chaobin;Huang, Xin;Li, Shengping
通讯作者：
Li, Shengping
影响因子：
4.6
作者：
Bhonsle, Suyashree;Lorenzo, Melvin F.;Davalos, Rafael, V
通讯作者：
Davalos, Rafael, V
影响因子：
--
作者：
Crile, GW;Hosmer, HR;Rowland, AF
通讯作者：
Rowland, AF