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. 2021 Nov 8;13(21):5583. doi: 10.3390/cancers13215583

Table 1.

Summary of some of the patient-derived xenograft HCC protocols in mice.

Model Procedure Animal (Species, Strain, Age) Timepoints and Incidence of Lesions References
Ectopic implantation of human HCC in mouse;
  • -

    Samples of human HCC were sectioned and inoculated on the dorsum of the mice; a region pretreated with anti-asialo GM1;

 Female Balb/c athymic nude mice at 4-week-old;
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    1st and 2nd generation: tumor growth at the implantation site with 100% (6/6) of transplantability and size averaged 1.0 cm in diameter at 4th week;

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    3rd generation: spontaneous liver metastasis at 12th week;

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    4th generation: 100% (5/5) of significant liver metastases in the 4th week;

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    8th week: all animals with transplanted tumors died with important metastases

 [26]
LCI-D20: orthotopic Implantation of human HCC
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    Tissue fragments measuring 2 mm3 of HCC from 30 human patients were implanted in the left hepatic lobe of the mice for 6 to 24 weeks;

 Male BALB/cA nude mice at 4 to 6-week-old
  • -

    At 2nd week: initial liver metastasis with tumor colonies around the site of origin;

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    At 3rd: metastasis in mesenteric and iliac lymph nodes, hepatic hilum, mesentery and diaphragm; micrometastasis in pulmonary vessels;

  • -

    At 6th week: generalized liver metastasis with vascular micrometastasis; micrometastasis in the lung parenchyma;

 [22]
HCC cells
  • -

    Different human HCC cells were cultured and suspended in saline solution at 1.108 cells/mL; afterward, 20 µL of cell suspension was injected into the mice’s liver subserosa.

 Male SCID at 6-week-old;
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    At 6–7th week: the necropsy of the implanted animals was performed or before that period, if they showed signs of stress;

  • -

    At 7th week: 2 of 12 cell lines had formed tumors only in the muscle; 5 of 12 cell lines had formed tumors in both muscles and lives; other 5 cells line did not form a tumor;

  • -

    Intrahepatic metastases observed in 2 of 12 explored cells line (Li7; KYN-2), with the presence of neoplastic thrombi and new neoplastic sites distinct from the original or in the lobe that did not undergo implantation.

 [23]
HCC-LY5 and HCC-LY10: Ectopic and orthotopic Implantation of human HCC in mice;
  • -

    Ectopic procedure: tissue fragments measuring 2 mm3 of HCC from human patients were transplanted in the subcutaneous tissue of the right flank of the mice. Tumor growth was measured once a week by palpation; when the tumor mass reached 10–15 mm, the tumor was removed, reimplanted in other mice, three more times;

  • -

    Orthotopic procedure: fragments of ectopic models were implanted in the left lobe of nude mice;

 NOD/SCID male and female mice and T cell-immunodeficient BALB/c-nu/nu mice at 6 to 8-week-old
  • -

    Ectopic implantation:

  • -

    At 4th week: the necropsy of the implanted animals was performed.

  • -

    5 of 24 human HCC samples were transplantable (20.83%);

  • -

    The growth rate of the tumor and the growth time increased according to the advance of the passages. Variable growth over 7–6 weeks (tumors with 2.7 mm3 to 7.2 mm3);

  • -

    Orthotopic implantation:

  • -

    At 6th week: the necropsy of the implanted animals was performed.

  • -

    The rate of tumor formation was 100% (8/8).

 [27]
Ectopic implantation from human HCC needle biopsies in mice
  • -

    10 human HCC needle biopsies from patients were transplanted into the subcutaneous tissue of the mice

 Nonobese, diabetic/severe combined immunodeficiency gamma-c mice at 10-week-old;
  • -

    11 PDX models were established with 10 human HCC needle biopsies.

  • -

    4th to 28th week after implantation, it was the time necessary to observe tumor growth;

  • -

    PDX subcutaneous injection of a biopsy cell suspension has a slow growth compared to intact tumor architecture;

  • -

    Retransplanted tumors showed a shortened lag phase until the onset of tumor growth compared to the xenograft tumor derived from the biopsy tissue;

 [24]