Multipotent mesenchymal stromal cells: A promising strategy to manage alcoholic liver disease

Table 2 Preclinical studies using mesenchymal stem cells or their derivatives to treat liver injury

Model animal species	Liver injury induction/kind of liver injury	MSCs administration route	Number andsource of transplanted MSCs	Therapeutic effect	Proposed mechanisms	Ref.
Rat	Allyl alcohol (ip administration)/chronic damage	Intrahepatic	1 × 106 MSCs from human BM	Hepatocyte regeneration	Hepatocyte differentiation without evidence of cell fusion	[76]
Mouse	Low-level of radiation/minimal, hepatic damage	Tail vein	2 × 104 MSCs from mouse BM	Hepatocyte regeneration	Hepatocyte differentiation	[78]
Mouse	Chronic exposure to high fat diet/NASH	Tail vein	0.5 × 106 MSCs from mouse BM	Prevention of NASH onset	Paracrine promotion of hepatic proliferation	[110]
				Preclusion of the inflammatory process	Increase in the fatty-acid oxidation enzymes expression
Mouse	Chronic exposure to atherogenic diet/NASH	Splenic capsule	0.1 × 106 MSCs from mouse adipose tissue	Restoration of albumin expression in hepatic parenchymal cells	Modulation of inflammation	[111]
				Amelioration of fibrosis	Increase in MMP expression
				Suppression of persistent hepatic inflammation
Mouse	CCl4 (ip administration)/liver fibrosis	Spleen	0.5 × 106 MSCs from human amniotic membrane	Reduction of liver fibrosis	Inactivation of HSCs	[126]
				Improvement of hepatic function	Reduction of hepatocyte apoptosis
					Promotion of liver regeneration
					Differentiation of hepatocyte-like cells
Mouse	CCl4 (ip administration)/liver fibrosis	Tail vein	0.5 × 106 MSCs from human BM	Reduction of liver fibrosis	Induction of MMP-9 expression	[121]
					Reduction in TGF-β expression
Rat	D-galactosamine (ip administration)/fulminant hepatic failure	Penile vein	Conditioned medium from human BM MSCs	Reduction in the mortality rate	Modulation of the immune response	[105,122]
				Reduction in panlobular leukocyte infiltrates	Trophic factor release (i.e., VEGF, HGF, and IGF-BP)
				Reduction in hepatocellular death
Mouse	CCl4 (ip administration)/liver fibrosis	Intrahepatic	Exosomes derived from human umbilical cord MSCs	Recovery of serum aspartate aminotransferase activity	Not determined	[109]
				Decrease in collagen type I and III, TGF-β1 level

BM: Bone marrow; HGF: Hepatocyte growth factor; HSC: Hepatic stellate cell; IGF-BP: Insulin-like growth factor-binding protein; ip: Intraperitoneal; MMP: Matrix metalloproteinase; MSC: Mesenchymal stem cell; NASH: Nonalcoholic steatohepatitis; TGF-β: Transforming growth factor-β; VEGF: Vascular endothelial growth factor.