Table 5 Humanized mouse models of hepatocellular carcinoma

Rhim et al. [99]

Hepatocyte transplantation model

EL-myc or MT-lacZ transgenic mice

10⁴ donor cells isolated from the livers of 6 to 8-week-old adult EL-myc or MT-lacZ transgenic mice were injected into the spleens of 5-11-day-old Alb-uPA recipient mice. Four to six weeks after transplantation, the recipient mice were euthanized by cadmium injection.

Azuma H et al. [100]

Hepatocyte transplantation model

Fah–/–/Rag2–/–/Il2rg–/– (FRG) mice

The mice were maintained with drinking water containing NTBC at a concentration of 16 mg/L. The hepatocytes were then transplanted into the recipient mice intraperitoneally after intravenous injection of 5 × 10⁹ units adenoviral vectors expressing human uPA. After transplantation, the concentration of NTBC was gradually reduced (1.6 mg/L on days 0–2, 0.8 mg/L on days 3–4, and 0.4 mg/L on days 5–6), and completely withdrawn one week after transplantation.

Zhou et al. [101]

Liver cancer, lymphocyte transplantation model

NOD/SCID mice

Mice were injected subcutaneously in the armpit with 1 × 10⁷ HepG2 cells which were mixed with equal volumes of Matrigel matrix. After 14 days of subcutaneous injection of HepG2 cells, the mice with grafted tumors were injected intraperitoneally with 2 × 10⁷ human peripheral blood lymphocytes from healthy populations. After 4 weeks, all mice were sacrificed.

Ito et al. [87],

Bhargavan et al. [102]

PBL transplantation model

NOD/SCID mice

The mice (4 to 6 weeks old males) were engrafted by intra-peritoneal (i.p.) injection of human PBL (30 × 10⁶ cells/mouse). For infection, a single dose of 10⁴ tissue culture infectious doses-50 (100 µl) of HIV-1ADA was intraperitoneally injected (i.p.) into animals. Animals were sacrificed after 3 weeks.

Traggiai et al. [90],

King et al. [103]

PMBC transplantation model

NOD/SCID mice

Mice were irradiated with 2 Gy 4 h prior to intravenous injection of varying doses of PBMC (5–20 × 10⁶ cells). After transplantation, euthanasia was performed when xenogeneic GVHD-like symptoms occurred.

Shultz et al. [88],

Holyoake et al. [104]

Bone marrow, hepatocyte transplantation model

NOD/SCID mice

Mice, aged 6 to 8 weeks, were sublethally irradiated with 350 cGy from a 137Cs source 24 h before receiving an intravenous injection of human bone marrow cells or liver cells. Additionally, mice received six consecutive intraperitoneal injections of human growth factors over a 2-week period before sacrifice.

Hayakawa et al. [105]

Cord blood transplantation model

NOD/SCID mice

Conditioning of Male NOD/SCID were 7–10 weeks old mice for Transplantation. Doses of 10 and 25 mg/kg of busulfan were injected 24 h before infusion of human cells. Donor human CB cells were suspended in PBS to final volume of 500 uL and infused intravenously via tail vein.

Czechowicz et al. [106]

Lan et al. [107]

Thymus, liver transplantation model

NOD/SCID mice

The mice, aged 6 to 10 weeks, were subjected to sublethal whole-body irradiation (2–3 Gy) as a preconditioning step. Within 3 days after irradiation, approximately 1 mm³ fragments of fetal thymus and liver were implanted under the recipient mice’s kidney capsule. After 6 weeks of human tissue transplantation, split thickness (2.2 mm) porcine skin samples were grafted onto the lateral thoracic wall of the mice. The skin grafts were assessed daily from day 7 onward up to 4 weeks, and thereafter, assessment was conducted every 3 days. Graft rejection was defined as less than 10% of the graft remaining viable.

Melkus et al. [108]

Thymus, liver transplantation model

NOD/SCID mice

6 to 8-week-old mice were anesthetized and surgically implanted with human fetal thymus and liver tissues under the kidney capsule. Three weeks after implantation, we subjected the mice to irradiation (325 cGy) from a 137Cs gamma radiation source. Subsequently, the mice were euthanized.