Table 2.
Animal models frequently used in CCA and their characteristics.
| Model name | Generation | Characteristics | Advantages | Disadvantages |
|---|---|---|---|---|
| Cell line-based Xenograft models | Cell lines got transplanted into mice (Subcutaneously or Orthotopically) | Imitate tumors in advanced stage. | Short experimental cycle; Low cost; Most commonly used; |
No immune microenvironment |
| Patient-derived Xenograft models | Patients’ tissue got transplanted into mice (Subcutaneously or Orthotopically) | Imitate tumors in advanced stage. | Recapitulate the heterogeneity of tumor | No immune microenvironment; |
| Genetically engineered mice (GEM) model/Reference | ||||
| Smad4-Pten model (62) | Smad4co and PTENco with Alb-cre mice | Imitate tumor at different stage. Bile duct hyperplasia at 2 months; Tumor development at 4–7 months |
Similar to human iCCA; | Mixed HCC-CCA phenotype; No inflammation; No chronic liver injury; No metastases |
| Kras-IDH model (63) | mIDH2, mKRAS with Alb-Cre mice. | Imitate tumor at different stage; tumors appear at 33–58 weeks |
Similar to human iCCA; Spontaneous metastases |
Long latency time |
| KRas-Pten model (64) | mKRas, PTENflox with alb-Cre mice | Imitate tumor at different stage; Multiple tumor nodules |
Similar to human iCCA; Short tumor latency |
No chronic liver injury; No metastases. No inflammation |
| KRas-P53 model (65) | mKrasG12D, p53 deletion with alb-Cre mice | Imitate tumor at different stage; Tumors appears at 9 weeks of age |
Similar to human iCCA; Spontaneous metastases |
No chronic liver injury; No inflammation; |
| ErbB model (66) | Bovine Keratin 5 (BK5) promoter-mediated constitutive expression of ErbB2. | Imitate tumor at different stage; iCCA appears at 4 months |
Similar to human iCCA; | Long latency time Gallbladder carcinoma model; |
| Notch1 model (67) | Alb-Cre mice with constitutive overexpression of Notch1 | Imitate tumor at different stage; | Homoplastic transplantation | Mixed HCC-CCA phenotyp; Long latency time |
| Tp53−/− CCl4 model (62) | Tp53−/− mice treated with CCl4 | Imitate tumor at different stage; iCCA development in 54% of mice. Injury and fibrosis in bile duct after 4 months of treatment |
Chronic liver injury; fibrosis and inflammation |
Development of HCC; Long treatment with CCl4 |
| Hydrodynamic Tail Vein Injection (HTVI) Models/Reference | ||||
| Yap and PI3KCA model (68) | Sleeping Beauty transposon toolbox, Yap and PI3KCA plasmid Injected into wt mice | Imitate tumor at different stage; | iCCAs cover ~80% of the liver parenchyma within 12–13 weeks post-HTVI |
Mixed HCC-CCA phenotype |
| NICD1 and AKT model (69) | Sleeping Beauty transposon toolbox, NCID1 and Akt plasmid Injected into wt mice | Imitate tumor at different stage; iCCA appears 4.5 weeks after HTVI |
Similar to human iCCA | Not mentioned |
| AKT and YAP model (70) | Sleeping Beauty transposon toolbox, AKT and YAP plasmid Injected into wt mice | Imitate tumor at different stage; | Similar to human iCCA | Relatively low successful rate |