Table 7.

Animal models of the use of mesenchymal stem cells isolated from human umbilical cord (hUC-MSC/(hWJ-MSC), their exosomes (EVs) and umbilical cord blood (hUCB-MSC) in the treatment of liver failure

Host	Number of cells or exosomes per one individual	Experimental model	Results	Ref.
human umbilical cord mesenchymal stem cells (hUC-MSC/(hWJ-MSC)
Rat	5 × 106	Dimethylnitrosamine-induced liver fibrosis	Decreased: ALAT and ASPAT plasma levels, and fibrosis, cholestasis, collagen deposition in the liver; Increased: mobilization of Kupffer cells, transition from M1 to M2 phenotype, and IL-10 and IL-4 plasma levels.	[156]
	5 × 106	Chronic injury – CCl4	Decreased: expression of α-SMA, TIMP-1, collagen type I and III, and ALAT, ASPAT and plasma bilirubin levels; hepatocyte swelling, necrosis, steatosis and centers of regeneration; Increased: expression of vimentin, E-cadherin, α-catenin and MMP-13, and ALB concentration.	[157]
	3 x 106 hUC-MSC ------------- 2.85-3mg hUC-MSC-EVs	Ischaemia/reperfusion (I/R) injury	Decreased: ALAT, ASPAT, ALP, IL-1β, IL-6, and TNFα in plasma, hepatocyte necrosis, number of hepatic infiltrating neutrophils, expression of caspase 3 and mitochondrial reactive oxygen species levels, serum serum IL-1β, IL-6, and TNFα levels (all in both groups - hUC-MSC-treated and hUC-MSC-EVs-treated) Decreased: mRNA levels for IL-1β, IL-6, TNFα, CC motif ligand 12, IFN-γ and TLR4 (in hUC-MSC-EVs-treated group)	[142]
	2.2-2.5 x 106	Acute injury - D-GalN (1000 mg/kg b.w.) and LPS (10μg/kg b.w.)	Decreased: ALAT, ASPAT and bilirubin in plasma, hepatocyte necrosis and inflammation, number of apoptotic hepatocytes; Increased: number of proliferating hepatocytes.	[158]
	1 x 106	Acute injury – CCl4	Decreased: ALAT, ASPAT and bilirubin levels in plasma, inflammation, cell degeneration and necrosis.	[133]
Mouse	5 × 106	Acute injury - acetaminofen i.p. 500mg/kg b.w.	Decreased: ALAT, ASPAT, ALP, GGTP and bilirubin in plasma, interstitial inflammation.	[159]
	3-5 x 106	Acute injury - CCl4	Decreased ALAT, ASPAT and bilirubin levels.	[160]
	2 x 106	Chronic injury – CCl4	Decreased: ALAT and ASPAT plasma levels, COL1, COL3, TGF-β1 mRNA expression, inflammation and swelling of liver cells, damage to mitochondria and parenchyma; Increased: TGFα mRNA expression.	[161]
	1 × 106	Ischaemia/reperfusion (I/R) injury	Decreased: ALAT and ASPAT in plasma, severity of damage.	[162]
	5 x 105	Fulminant injury – D-GalN	Decreased: number of necrotic cells and inflammatory response cells, reduced liver damage, extended survival time of animals.	[163]
	2.5 x 105	Acute injury – CCl4	ALAT, MCP-1 and IP-10 serum levels were not significantly changed indicating lack of therapeutic effect of stem cells.	[164]
human umbilical cord blood mesenchymal stem cells (hUCB-MSC)
Mouse	1 x 106	Chronic injury – CCl4	Decreased: bilirubin level, expression of ITGB1 and COL1A1, number of SMA(+) cells and parenchymal fibrosis; Increased: albumin synthesis.	[165]