Copyright ©The Author(s) 2019.
World J Gastroenterol. Jul 7, 2019; 25(25): 3136-3150
Published online Jul 7, 2019. doi: 10.3748/wjg.v25.i25.3136
Table 4 Available techniques for induction of hepatocellular carcinoma in relation to temporal and technical aspects as well as major advantages and disadvantages (summarized from[92])
Method and specificationTime to HCCshort (+) to long (+++)Technical effortslow (+) to high (+++)Major “Pros” (+) vs “Contras” (-)
Chemotoxic agents linked models
Diethylnitrosamine+++(+) good combination options with other methods
9,10-dimethyl-1,2-benzanthracene(-) time to HCC not easily predictable
Direct implantation of tumor cells or tissue
Heterotopic/orthotopic++/++(+) heterotopic xenografts are often and easily done
(+) syngeneic orthotopic models better reflect the natural liver microenvironment
Syngeneic/xenografts(-) xenografts need immunocompromised mice
(-) orthotopic tumor implants need surgical and imaging experience
Genetically engineered mouse models
Mouse embryo manipulation++/++++++(+) hepatocarcinogenesis can be analyzed stepwise
Cre-Lox recombination(-) effects of manipulated gene(s) could have heterogeneous latency and genetic penetrance
Hydrodynamic injection
Humanized mouse models
Immunologically humanized mice++++++(+) immunotherapeutical issues can be studied based on human cell lines in mice
Genetically humanized mice(-) establishment difficult due to engraftment failure and development of stable stem cell-derived hepatocytes