The Efficiency of Stem Cells (SCs) Differentiation into Functional Hepatocytes for Treating Liver Disorders: A Systematic Review

Table 2

Overview of in vivo differentiation efficacy of SCs into hepatic cells.

Cell source	Intervention (s)	Human/animals	Transplanted method	Outcome	Author (year)
MSCs	Cocultured with AML12 hepatocytes	CCl4 liver injury in rats	Implantation in liver	Significant reductions in AST and ALT levels; Promoting liver repair and liver tissue regeneration	[8]
BMSCs	Transplantation	Mice with hepatic failure		Cholangiocytes can be efficiently differentiated from BMSCs	[25]
BMSCs	Cultured with HGF	Patients with end-stage liver cell failure	Intrasplenic or intrahepatic injection	Significant improvement in serum ALB; The results demonstrated the short-term efficacy of SCs injection in liver cell failure.	[45]
BMMSCs	Transplantation	CCl4 liver injury in mice	Tail vein injection	Decreased AST and ALT; Increased ALB concentration; Improved liver regeneration	[40]
ADSCs	Transplantation	Rats with partial hepatectomy	Portal vein or hepatic parenchyma injection	Significant higher liver regeneration rate; Upregulated the expression of hepatic specific markers	[43]
ADMSC	Transplantation	CCl4 liver injury in mice	Tail vein injection	Prolonged recipient survival; Produced ALB and CK-18	[41]
UMSC-CM	Transplantation	CCl4 liver injury in rats	Intravenous injection	Improved oxidative status; Increased expression of hepatic specific gen and protein level	[38]
UMSC-CM	Transplantation	CCl4 liver injury in rats	Intravenous injection	Improved oxidative status; Increased expression of hepatic specific gen and protein level	[39]
WJMSCs	Transplantation	CCl4 liver injury in rats		Decreased liver fibrosis and fibrotic related genes	[14]
ESCs	Transplantation	Mice with liver injury	Intrasplenic injection	The resulted cells, clonally expanded hepatic progenitor cells repopulated the livers of fah-deficient mice without inducing tumorigenesis	[47]
ESCs	Transplantation	CCl4 liver injury in mice	Intrasplenic injection	Integrated into the liver and expressed α-1 antitrypsin	[21]
iPSCs	Transplantation	Mice with ALF	Intrahepatic injection	Prolonged recipient survival	[48]
iPSCs	Multistage differentiation protocol	Mice with liver cirrhosis	Intraperitoneal injection	Successful repopulation of the liver tissue, also secretion of human-specific liver proteins into mouse blood	[50]
iPSCs	Transplantation of differentiated cell cultured on recombinant laminin	Inherited liver disease model rats	Splenic injection	Significant bilirubinemia reduction	[46]
hPSCs	Implantation	Acute liver injury mouse		These results demonstrated the significant impact of differentiation fate and differentiation efficacy	[37]
MenSCs	Transplantation	CCL4 liver injury mice	Tail vein injection	Significant liver function improvement; Attenuated collagen deposition	[9]
MenSCs	Transplantation	Pig with ALF	Portal vein injection	Significant reduction of of ALT, AST, TB, and PT levels; Prolonged recipient survival	[44]
FLCs	Transplantation	Mice with ALF	Intrasplenic injection	Expressed ALB, AFP, CK-19, and antitrypsin mRNA	[1]
HSCs	Transplantation of HSCs	Noninjury sheep model of liver cell deficiency	IP transplantation	Efficiently generated functional hepatocytes secreting ALB	[49]
HSCs	Transplantation	CCL4 liver injury mice	Tail vein injection	Regenerated of injured liver by differentiating into functional hepatocytes	[42]
HSLc	Transplantation on type I collagen matrices	Analbuminemic rat	Intraliver injection	Increased in the serum ALB 2.5-fold compared to control group	[16]
Human liver SC line (HYX1)	Transplantation	Mice with ALF	Intraperitoneal	Decreased level of ALT, AST, TB, and liver injury	[52]

MSC: Mesenchymal stem cell, CCL4: Carbon tetrachloride, AST: Aspartate transferase, ALT: Alanine transferase, BMSC: Bone Mesenchymal stem cell, HGF: Hepatocyte growth factor, ALB: Albumin, BMMSC: Bone marrow mesenchymal stem cell, ADSC: Adipose derived stem cell, ADMSC: Adipose derived mesenchymal stem cell, CK: Cytokeratin, UMSC-CM: Umbilical mesenchymal stem cell-condition media, ESC: Embryonic stem cell, iPSC: induced pluripotent stem cell, ALF: Acute liver failure, MenSC: Menstrual stem cell, TB: Total bilirubin, PT: Prothrombin time, FLC: Fetal liver progenitor cell, AFP: Alfa Phyto protein, HSC: Hematopoietic stem cell, HSL: Liver epithelial cell line.