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Development and Characterization of Human-Derived Xenograft Model for Hepatocellular Carcinoma

M. Nazzal1, R. Steele2, R. Ray3, N. Phillips2, J. Long4, R. Ray2

1Surgery, Saint Louis University, Saint Louis, MO, 2Pathology, Saint Louis University, Saint Louis, MO, 3Internal Medicine, Saint Louis University, Saint Louis, MO, 4Comparative Medicine, Saint Louis University, Saint Louis, MO

Meeting: 2019 American Transplant Congress

Abstract number: 66

Keywords: Hepatitis C, Hepatocellular carcinoma, Malignancy, Mice

Session Information

Session Name: Concurrent Session: Tissue Engineering & Technology

Session Type: Concurrent Session

Date: Sunday, June 2, 2019

Session Time: 2:30pm-4:00pm

 Presentation Time: 3:30pm-3:42pm

Location: Room 309

*Purpose: Hepatocellular carcinoma (HCC) is rising in the USA and treatment options are limited. There is no convenient animal model for HCC to study novel treatment potential. The goal of our study is to develop patient-derived xenograft (PDX) model from human HCC specimen with different etiology and evaluate treatment options.

*Methods: To address this, viable tumor tissues were collected after resection of tumor from patients and implanted into highly immunodeficient NSG mice.

*Results: We successfully developed two mouse lines: one from NASH patient, and the other one from HCV associated HCC patient. We successfully passaged the primary mouse tumors at least for two rounds in immunodeficient mice. Histological analysis suggested that HCC present in mouse tumors were similar to patient tumor. The presence of human albumin, glypican3 and alpha-1-antitrypsin markers of human hepatocyte origin was noted in human tissues used in implantation and passaged xenograft tumors. Interestingly, HCV RNA detected from patient liver specimens was undetectable in passaged xenograft tumors, suggesting that the human liver environment may be important for HCV replication. Biochemical analysis indicated that tumor specimens from patients display the presence of human fibrosis markers. However, tumor grown in mice exhibited mouse fibrosis marker only, implying species specific tumor associated fibroblast migration in the respective tumor regions.

*Conclusions: We were able to successfully create a patient-derived xenograft (PDX) model from human HCC specimen .We are in the process of establishing HCC cell lines and performing genetic profiling for comparison of human and mouse grown xenograft

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To cite this abstract in AMA style:

Nazzal M, Steele R, Ray R, Phillips N, Long J, Ray R. Development and Characterization of Human-Derived Xenograft Model for Hepatocellular Carcinoma [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/development-and-characterization-of-human-derived-xenograft-model-for-hepatocellular-carcinoma/. Accessed May 11, 2025.

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