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Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their sm...

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Autores principales: Mishima, Kohei, Itano, Osamu, Matsuda, Sachiko, Suzuki, Shunichi, Onishi, Akira, Tamura, Masashi, Inoue, Masanori, Abe, Yuta, Yagi, Hiroshi, Hibi, Taizo, Kitago, Minoru, Shinoda, Masahiro, Kitagawa, Yuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984615/
https://www.ncbi.nlm.nih.gov/pubmed/33750947
http://dx.doi.org/10.1371/journal.pone.0248352
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author Mishima, Kohei
Itano, Osamu
Matsuda, Sachiko
Suzuki, Shunichi
Onishi, Akira
Tamura, Masashi
Inoue, Masanori
Abe, Yuta
Yagi, Hiroshi
Hibi, Taizo
Kitago, Minoru
Shinoda, Masahiro
Kitagawa, Yuko
author_facet Mishima, Kohei
Itano, Osamu
Matsuda, Sachiko
Suzuki, Shunichi
Onishi, Akira
Tamura, Masashi
Inoue, Masanori
Abe, Yuta
Yagi, Hiroshi
Hibi, Taizo
Kitago, Minoru
Shinoda, Masahiro
Kitagawa, Yuko
author_sort Mishima, Kohei
collection PubMed
description Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6–15.6 kg) via ultrasonography-guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC.
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spelling pubmed-79846152021-04-01 Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model Mishima, Kohei Itano, Osamu Matsuda, Sachiko Suzuki, Shunichi Onishi, Akira Tamura, Masashi Inoue, Masanori Abe, Yuta Yagi, Hiroshi Hibi, Taizo Kitago, Minoru Shinoda, Masahiro Kitagawa, Yuko PLoS One Research Article Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6–15.6 kg) via ultrasonography-guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC. Public Library of Science 2021-03-22 /pmc/articles/PMC7984615/ /pubmed/33750947 http://dx.doi.org/10.1371/journal.pone.0248352 Text en © 2021 Mishima et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mishima, Kohei
Itano, Osamu
Matsuda, Sachiko
Suzuki, Shunichi
Onishi, Akira
Tamura, Masashi
Inoue, Masanori
Abe, Yuta
Yagi, Hiroshi
Hibi, Taizo
Kitago, Minoru
Shinoda, Masahiro
Kitagawa, Yuko
Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model
title Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model
title_full Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model
title_fullStr Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model
title_full_unstemmed Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model
title_short Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model
title_sort development of human hepatocellular carcinoma in x-linked severe combined immunodeficient pigs: an orthotopic xenograft model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984615/
https://www.ncbi.nlm.nih.gov/pubmed/33750947
http://dx.doi.org/10.1371/journal.pone.0248352
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