Reference |
Animal model |
Type and number of transplanted cells |
Percentage of repopulation |
Improved liver functions |
Mouse survival after transplantation |
Teratani et al. [118] |
129X1/SvJ and BALB/c nude mice (DMN, cirrhosis) |
mESC-Hep 5 e6/mouse (IV) |
ND |
Suppression of onset of fibrosis/cirrhosis plasma fibrinogen Alb |
~40% after 12 weeks |
Heo et al. [116] |
MUP-uPA/SCID + CCL4 |
mESC-Hep 1 e6/mouse (IS) isolated Alb+ cells |
1.94% +/- 5.81 after 82 days |
ND |
ND |
Gouon-Evans et al. [50] |
Dpp4-/-, Rag2-/- (CCl4 and retrorsine) and Fah-/- |
mESC-Hep 0.25 - 1.5 e6/mouse (IS) |
Scattered endothelial and hepatocytic clusters |
ND |
ND |
Agarwal et al. [121] |
NOD/SCID (CCl4 and retrorsine, acute liver failure) |
hESC-Hep 1 e6/mouse (PV) |
sporadic hepatocytic clusters |
ND |
ND |
Hay et al. [26] |
NOD/SCID |
hESC-Hep 1 e6/mouse (IS) |
Clusters of CK18/CK19 and Alb cells after 3 days in the spleen |
Alb |
|
Cai et al. [25] |
SCID (CCl4, acute liver failure) |
hESC-Hep 1 e6/mouse (IS) |
scattered AAT human cells in livers |
ND |
ND |
Duan et al. [122] |
NOD/SCID |
hESC-Hep 0.5 e6/site (IH) |
ND |
Alb |
ND |
Haridass et al. [114] |
Alb-uPA, Rag2-/-, IL2Rγ-/- |
ES-Hep 0.5-1 e6/mouse (IS) |
Few cells scattered and teratoma formation |
ND |
ND |
Basma et al. [115] |
NOD/SCID (retrorsine and 50% hepatectomy) Alb-uPA SCID |
hES-Hep 0.1-0.2 e6/mouse (IS) Isolated ASGPR+ cells |
Few clusters of albumin+ cells after 28 days |
Alb, AAT |
ND |
Li et al. [78] |
Fah-/- |
mES-Hep 1 e6/mouse (IS) Isolated ckit-Epcam+ |
24%+/-15% |
ND |
at least 10 weeks |
Touboul et al. [27] |
Alb-uPA, Rag2-/-, IL2Rγ-/- |
hES-Hep 0.5 e6/mouse (IH) |
Small and large clusters throughout the liver after 8 weeks |
AAT Alb |
ND |
Si-Tayeb et al. [17] |
|
hiPSC-Hep 0.3 e6/mouse (IH) |
ND |
ND |
ND |
Huang et al. [102] |
Fah-/-, Rag2-/- |
m iHep from fibroblasts 0.833 e6/mouse (IS) |
5%-80% |
ALT, AST, Tyrosine, Phenylalanine, Bilirubin |
5/12 mice survived after 8 weeks |
Sekiya and Suzuki [103] |
Fah-/- |
m iHep from fibroblasts (IS) |
Large clusters of |
Bilirubin, ALT, ALP, Alb |
40% at 10 weeks |
Li et al. [119] |
BALB/c nude (TAA, liver fibrosis) |
m iPSC-Hep ~0.25 e6/mouse (IV) |
Scattered cells in the liver after 24h00 |
ALT, AST, Bilirubin, Ammonia, decreased ROS levels and necrosis |
~80% after 14 days |
Chang et al. [117] |
BALBc nude (CCl4, acute liver failure) |
m iPSC-Hep 0.2-5 e6/mouse (IP) |
Necrosis : 70% control, 20% transplant |
ALT, AST, Bilirubin |
90% at 14 days |
Woo et al. [39] |
BALBc nude (CCl4, acute liver failure) |
hES-Hep / hiPSC-Hep 2 e6/mouse (IS) Isolated ICG+ cells |
~20% at day 3 versus ~10% after 35 days |
Alb |
ND |
Chen et al. [38] |
NOD/SCID (CCl4, acute liver failure) |
hiPSC -Hep (IS) |
ND |
rescue of hepatic necrosis glutamyl oxaloacetic aminotransferase glutamyl pyruvic aminotransferase Bilirubin lactate dehydrogenase HepPar1 Alb |
5/7 (71%) after 21 days |
Liu et al. [41] |
NSG (DMN, cirrhosis) |
hiPSC-Hep 0.1-2 e6/mouse (IV) |
2 to 17% |
Alb, CYP2E1 |
90% after 8 weeks |
He et al. [113] |
Fah-/- |
mESC-Hep (IS) |
0.001%-12.5% after 8-10 weeks |
ALT, AST, Bilirubin, Alb, succinylacetone, tyrosine and phenylalanine secretion 30% of wt FAH activity in recipients |
8/20 survived after 2nd transplantation |
Bandi et al. [120] |
CD17.NOD/SCID (Rif + Phen + MCT, acute liver failure) |
hESC-MEC 4-6 e6/mouse (IP with microcarriers) |
Detection of transplanted cells in the peritoneal cavity |
Endogeneous hepatocytes proliferation Phenobarbital metabolism Ammonium chloride |
11/11 after 14 days (MCT 125, mild injury) 38% after 2 weeks (MCT 160, strong injury) |
PSC: pluripotent stem cell, IV: intra venous injection; IS: intra splenic injection; IH: intra hepatic injection; IP: intra peritoneal injection; hESC-MEC: hESC meso-endodermal
cells. Detection in serum of Alb (Albumin), AAT (alpha 1 anti-trypsin), ALT (alanine aminotransferase), AST (aspartate aminotransferase), bilirubin, AP (Alkaline phosphatase)
and CYP2E1 activity.