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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 11
Nov.  2021
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Article Contents

Construction of a new patient-derived xenograft model of human liver cancer in mice with normal immunity

DOI: 10.3969/j.issn.1001-5256.2021.11.019
Research funding:

National Natural Science Foundation of China (81170395);

National Natural Science Foundation of China (81570556);

Chinese foundation for hepatitis prevention and control—TianQing liver disease research fund subject (TQGB20210013);

National Key R&D Program of China (2017YFA0103000);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Preventon and Treatment" (2017ZX10203201-005);

Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201806)

  • Received Date: 2021-04-13
  • Accepted Date: 2021-05-24
  • Published Date: 2021-11-20
  •   Objective  To establish a new patient-derived xenograft (PDX) model of human liver cancer by inoculating the complex of human primary liver cancer cells and a novel microcarrier (microcarrier 6) into mice with normal immune function.  Methods  Primary liver cancer cells were isolated and extracted from the fresh human liver cancer tissue of five patients and were then co-cultured with microcarrier 6 to construct a three-dimensional tumor cell culture model in vitro. According to the type of graft, 75 male C57BL/6 mice were divided into cell control group, microcarrier control group, and experimental group (each sample corresponded to three groups, with 15 groups in total and 5 mice in each group). The liver cancer cell-microcarrier complex was implanted into the mice by subcutaneous inoculation, and tumor formation time, tumor formation rate, and histopathological manifestations were observed. The Fisher's exact test was used for comparison of categorical data between two groups.  Results  As for the liver cancer cells from the five patients, tumor formation was observed in the mice corresponding to three patients. In these three experiments, tumor formation was not observed in the control groups and was only observed in the experimental groups, and 12 of the 15 mice in the experimental groups had successful tumor formation, with a tumor formation rate as high as 80%, which was significantly different from that in the cell control groups and the microcarrier control groups (all P < 0.05). The tumor formation time was 5-7 days; the xenograft tumor grew rapidly, and HE staining showed nested or flaky cells with obvious heteromorphism, with the presence of pathological mitosis; immunohistochemical staining showed positive CK8/18, Hep, and Gpc-3, which was in accordance with the characteristics of human liver cancer cells.  Conclusion  This experiment successfully establishes a new PDX model of human liver cancer based on the complex of microcarrier 6 and human primary liver cancer cells in mice with normal immunity. This model can be used to better elucidate the mechanism of the development and progression of liver cancer in the body with normal immunity, and besides, it also provides a new animal model with higher value for the precise treatment of liver cancer.

     

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