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利用脾切除术、胸腺切除术和口服免疫抑制法建立用于胰腺癌异种移植的免疫缺陷猪模型

Development of an Immunodeficient Pig Model for Pancreatic Cancer Xenotransplantation Using Splenectomy, Thymectomy, and Oral Immunosuppression.

作者信息

Lee Jun Suh, Yoon Yoo-Seok, Han Ho-Seong, Cho Jai Young, Lee Hae-Won, Lee Boram, Park Yeshong, Kang MeeYoung

机构信息

Department of Surgery, Bucheon Sejong Hospital, Bucheon 14754, Republic of Korea.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.

出版信息

Medicina (Kaunas). 2025 Mar 25;61(4):586. doi: 10.3390/medicina61040586.

DOI:10.3390/medicina61040586
PMID:40282876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12029007/
Abstract

: Animal models are widely used in medical research, but most are limited to small or medium-sized species due to logistical constraints. However, pancreatic cancer research and surgical xenograft models require large animals with anatomical similarities to humans and minimal immune rejection. This study evaluates the feasibility of an operative immunodeficient pig model for patient-derived xenografts. : During the period of October 2020 and October 2021, four pigs were used to establish a pig model at Seoul National University Bundang Hospital. A conventional pig 40 weeks of age was used. After introduction into the animal laboratory, splenectomy and thymectomy were performed to minimize B-cell and T-cell function. One week after the initial operation, oral immunosuppression was administered. After 4 weeks, human PDAC cells were implanted in the liver and pancreas. After 4 weeks of implant, the pigs were sacrificed, and the operative and pathologic findings were analyzed. : All four pigs survived the 9-week experiment. Indwelling venous catheters for drug-level monitoring were attempted but failed. Splenectomy and thymectomy were deemed to be feasible and effective. Oral immunosuppression was acceptable, but the initial dosage was better tolerated at low levels. Out of the four pigs, one pig showed a mass formation at the cell line injection site, demonstrating reactive cell clusters on pathology. : This pig model using conventional pigs is a feasible model of immunosuppression. It is necessary to fine-tune the oral immunosuppression dosage and develop methods for the frequent monitoring of immunosuppression levels.

摘要

动物模型在医学研究中被广泛使用,但由于后勤限制,大多数仅限于中小型物种。然而,胰腺癌研究和手术异种移植模型需要与人类解剖结构相似且免疫排斥最小的大型动物。本研究评估了用于患者来源异种移植的手术免疫缺陷猪模型的可行性。

在2020年10月至2021年10月期间,首尔国立大学盆唐医院使用4头猪建立了猪模型。使用了一头40周龄的常规猪。引入动物实验室后,进行脾切除术和胸腺切除术以尽量减少B细胞和T细胞功能。初次手术后一周,给予口服免疫抑制。4周后,将人胰腺导管腺癌(PDAC)细胞植入肝脏和胰腺。植入4周后,处死猪并分析手术和病理结果。

所有4头猪都在为期9周的实验中存活下来。尝试放置用于药物水平监测的留置静脉导管,但未成功。脾切除术和胸腺切除术被认为是可行且有效的。口服免疫抑制是可以接受的,但初始剂量在低水平时耐受性更好。在这4头猪中,有1头猪在细胞系注射部位出现肿块形成,病理显示为反应性细胞簇。

这种使用常规猪的猪模型是一种可行的免疫抑制模型。有必要微调口服免疫抑制剂量并开发频繁监测免疫抑制水平的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/e588221f0a1b/medicina-61-00586-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/caa98311303b/medicina-61-00586-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/ef43ec004ebe/medicina-61-00586-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/f630b92441e5/medicina-61-00586-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/e588221f0a1b/medicina-61-00586-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/caa98311303b/medicina-61-00586-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/ef43ec004ebe/medicina-61-00586-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/f630b92441e5/medicina-61-00586-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/12029007/e588221f0a1b/medicina-61-00586-g004.jpg

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Development of an Immunodeficient Pig Model for Pancreatic Cancer Xenotransplantation Using Splenectomy, Thymectomy, and Oral Immunosuppression.利用脾切除术、胸腺切除术和口服免疫抑制法建立用于胰腺癌异种移植的免疫缺陷猪模型
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本文引用的文献

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Effects of subtotal pancreatectomy and long-term glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs.部分胰腺切除术和长期糖脂过载对小型猪胰岛素分泌和糖稳态的影响。
Endocrinol Diabetes Metab. 2023 Jul;6(4):e425. doi: 10.1002/edm2.425. Epub 2023 May 5.
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Neoadjuvant therapy for pancreatic cancer.胰腺癌的新辅助治疗。
Nat Rev Clin Oncol. 2023 May;20(5):318-337. doi: 10.1038/s41571-023-00746-1. Epub 2023 Mar 17.
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Advances in pig models of human diseases.人类疾病猪模型的研究进展。
Animal Model Exp Med. 2022 Apr;5(2):141-152. doi: 10.1002/ame2.12223. Epub 2022 Mar 27.
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Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes.免疫缺陷猪模型的建立,使其能够长期容纳人工人血管管腔。
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Porcine Models of Pancreatic Cancer.胰腺癌的猪模型
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Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs.人卵巢癌在严重联合免疫缺陷(SCID)猪体内的肿瘤形成。
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Bilateral Axillo-Breast Approach to Endoscopic Thyroidectomy in a Porcine Model.猪模型中双侧腋窝-乳房入路内镜甲状腺切除术
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