Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms

Table 1 Clinical trials in liver diseases using human umbilical cord mesenchymal stem cells

Ref.	Administration route	Number of cells infused	Etiology or disease	Study design, n for total; groups	Follow-up period	Trial number	Results
[110]	Intravenous	(4.0-4.5) × 108	Decompensated liver cirrhosis	103; 50 hUC-MSCs, 53 control	52 wk	ChiCTR-ONC-12002103	Decrease in AST, increase in ALB, TBIL, PT Improvement in MELD and Child-Pugh scores
[56]	Intravenous	0.5 × 106/kg Every 4 wk, 3 times	ACLF (HBV cirrhosis)	43; 24 hUC-MSCs, 19 control	72 wk	NCT01218464	Improvement in MELD Increase in ALB, PT
[111]	Intravenous	0.5 × 106/kg Every 4 wk, 3 times	Cirrhosis (HBV)	45; 30 hUC-MSCs, 15 control	48 wk	NCT01220492	Decrease in ascites. Increase in ALB, TBIL. Improvement in MELD.
[112]	Intravenous	0.5 × 106/kg Every 4 wk, 3 times	UDCA-resistant PBC	7	48 wk	NCT01662973	Decrease in ALP, γ-GT, fatigue, pruritus Improvement quality of life
[113]	Intravenous	1 × 106/kg; wk 1, 2, 4, 8, 12 and 16	Ischemic-type biliary lesions	82; 12 hUC-MSCs, 70 control	96 wk	NCT02223897	Decrease in BIL, ALP, γ-GT Improvement in graft survival
[114]	Intravenous	1 × 106/kg; Every 4 wk, 3 times	Liver transplant patients with acute graft rejection	27; 14 hUC-MSCs, 13 control	12 wk	NCT01690247	Decrease in ALT, AST, TBIL, acute rejection Improvement in liver allograft histology
	Peripheral vein	4.0 × 107/patient, 4 times	LC	320	144 wk	NCT01573923	Unknown
	Unknown	Unknown	LC	20	48 wk	NCT01342250	Unknown
	Peripheral vein	1.0 × 105/kg, 4 times	Liver failure (HBV)	120	48 wk	NCT01724398	Unknown
	Portal vein or hepatic artery	Unknown	LC	200	48 wk	NCT01233102	Unknown
	Hepatic artery	Unknown	LC	50	4 wk	NCT01224327	Unknown
	Hepatic artery	1.0 × 106/kg	LC (HBV)	240	48 wk	NCT01728727	Unknown
	Peripheral vein			210	72 wk	NCT01844063	Unknown
	Peripheral vein	Unknown	ACLF (HBV)	261	52 wk	NCT02812121	Unknown
	Portal vein or hepatic artery	2.0 × 107/patient, 4 times	LC	20	48 wk	NCT02652351	Unknown
	Peripheral vein	1.0 × 106/kg, 3 times	Liver failure (AIH)	100	96 wk	NCT01661842	Unknown
	Lobe	5.0 × 108/patient	LC	40	96 wk	NCT02786017	Unknown

ACLF: Acute-on-chronic liver failure; AIH: Autoimmune hepatitis; ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine transaminase; AST: Aspartate transaminase; BIL: Bilirubin; γ-GTP: Gamma-glutamyl transpeptidase; HBV: Hepatitis B virus; LC: Liver cirrhosis; MELD: Model for end-stage liver disease; PBC: Primary biliary cholangitis; PT: Prothrombin time; TBIL: Total bilirubin; UCDA: Ursodeoxycholic acid.