Table 1.

Chimeric human liver mouse models (Part I).

Name	Alb-uPA/SCID	cDNA-uPA/SCID	MUP-uPA/SCID/Bg
Nomenclature	-	-	-
Engraftment method for humanization of immune system	-	-	-
Engraftment method for humanization of liver	Intrasplenic injection	Intrasplenic injection	Intrasplenic injection
Source of cells	Human hepatocyte	Human hepatocyte	Human hepatocyte
Presence of human hepatocytes	Yes	Yes	Yes
Presence of human immune system	No	No	No
Method of HCV infection	Intraperitoneal injection	Intravenous injection	Intravenous injection
Strain of HCV used	Patient serum containing HCV genotype 1a	Serum/culture medium of HCV (105 copies)	Diluted plasma from HCV-infected chimpanzee
Duration monitored post-HCV infection	Up to 10 weeks	Up to 8 weeks	Up to 8 weeks
Advantages	Presence of mature human hepatocytes This model is able to recapitulate the human immune system more efficiently than mouse models without humanization Higher human hepatocytes and HCV viraemia levels as compared to TK-NOG Useful for evaluation antiviral agents Capable of supporting long-term HCV infection	The cDNA with albumin promoter/enhancer and uPA demonstrate no loss of uPA due to the deletion of transgene Few renal disorders High body weight High survival rate Presence of mature human hepatocytes Higher hepatocyte reconstitution as compared to Alb-uPA/SCID mice Higher concentration of serum albumin as compared to Alb-uPA/SCID mice High and persistent titers of viremia Capable of supporting long-term HCV infection	Easy to maintain colony of transgenic mice High survival rate Less technically challenging to engraft hepatocytes into mice, as there is a long window to engraft mice (4-12 months) Each major HCV genotype was infectious in MUP-uPA/SCID mice Capable of supporting long-term HCV infection
Drawbacks	Poor breeding efficiency Short window for engraftment Absence of human immune system Liver environment is unsuitable for the engraftment of fetal-liver derived cells Unable to reproduce pathological outcomes of HCV Impossible to study HCV immunopathogenesis No liver disease Low level of hepatocyte reconstitution Low serum levels of human albumin and HCV viremia Repopulation of the liver with human cells may be cause by cell fusion No liver disease High mortality rate Low body weight High renal disorders	Absence of human immune system Unable to reproduce pathological outcomes of HCV Liver environment is unsuitable for the engraftment of fetal-liver derived cells Impossible to study HCV immunopathogenesis No liver disease	Absence of human immune system Variable viral replication observed in mice Unable to reproduce pathological outcomes of HCV Liver environment is unsuitable for the engraftment of fetal-liver derived cells Impossible to study HCV immunopathogenesis No liver disease
References	Washburn et al. (2011) [66] Steenbergen et al. (2010) [69]	Uchida et al. (2017) [70]	Tesfaye et al. (2017) [71] Carpentier et al. (2014) [72]

Abbreviations: cDNA: Complementary DNA, Fah: Fumarylacetoacetate hydrolase, HCV: Hepatitis C virus, NTBC: 2-(2-nitro-4-trifluoro-methylbenzoyl)1,3-cyclohexedione.