Table 1.

Transplantation of MSC-CM and exosomes is an effective therapy for attenuating acute or chronic liver injury via different mechanisms

Animal of origin	Tissue of origin	Type of MSC derivatives	Quantity	Route	Liver injury	Model	Effect	Mechanism	Ref.
Rat	Bone marrow	MSC-CM	1 ml (from 1 × 106 MSCs)	Penile vein	Radiation	Rat	Inhibit the apoptosis of SECs; inhibit histopathological changes	Attenuate liver inflammation	[79]
Rat	Bone marrow	25-fold concentrated MSC-CM	1 ml	Penile vein	50% RSLT	Rat	Attenuate liver injury; provide a survival benefit	Reduce apoptosis of hepatocytes and SECs; reduce the secretion of proinflammatory cytokines; reduce the infiltration of neutrophils; activation of Kupffer cells	[80]
Mouse	Bone marrow	25-fold concentrated MSC-CM	200 μl	Tail vein	TAA/CCl4	Mouse	Rescue ALF mice; suppress fibrogenesis	Downregulate the number of infiltrating macrophages; convert CD4+ T lymphocytes into anti-inflammatory Tregs and Th2 cells; facilitate HSC death	[81]
Human	Tonsil	20-fold concentrated MSC-CM	200 μl	Tail vein	CCl4	Mouse	Reduce liver fibrosis	Attenuate liver inflammation	[82]
Mouse	Bone marrow	Exosomes	10 μg	Intravenous	Con A	Mouse	Decrease the ALT level; decrease the scope of liver necrotic areas; decrease the extent of apoptosis; increase the proliferation of liver cells	Activate anti-inflammation; activate Tregs	[83]
Human	iPSCs	Exosomes	2.5 × 1012 particles	Inferior vena cava	Ischemia/reperfusion	Mouse	Decrease the histopathological scores and serum levels of aminotransferases	Inhibit hepatocyte necrosis and sinusoidal congestion; upregulate hepatocyte proliferation	[84]
Human	Umbilical cord	Exosomes	100 μg	Tail vein	D-GalN/LPS	Mouse	Repair damaged liver tissue; decrease serum levels of ALT and AST	Reduce the activity of the NLRP3 inflammasome in macrophages	[85]
Human	Menstrual blood	Exosomes	N/A	Tail vein	D-GalN/LPS	Mouse	Improve liver functions; inhibit hepatocyte apoptosis; increase survival rates	Migrate into liver tissue; reduce the activation of MNCs; decrease the level of the apoptotic protein caspase-3	[86]
Human	Umbilical Cord	Exosomes	6.4 × 109 particles	Tail vein	CCl4	Mouse	Decrease the rates of acute liver injury and liver fibrosis	Inhibit oxidative stress; inhibit hepatocyte apoptosis	[87]
Human	Bone marrow	Exosomes	250 mg	Tail vein	CCl4	Rat	Alleviate liver fibrosis	Inhibit HSC activation; activate the Wnt/β-catenin pathway	[88]
Human	Umbilical cord	25-fold concentrated MSC-CM	7.2 ml	Liver lobe	CCl4	Mouse	Ameliorate liver fibrosis; restore liver functions	Inhibit EMT; protect against hepatocyte apoptosis	[89]
Mice	Adipose tissue	Exosomes	400 μg	Tail vein	D-GalN/LPS	Mouse	Repair damaged liver tissue; decrease serum levels of ALT and AST	Reduce the activation of TXNIP/NLRP3 in macrophages	[90]
Human	Umbilical cord	Exosomes	8 mg/kg, 16 mg/kg, and 32 mg/kg	Tail vein	CCl4	Mouse	Rescue ALF; increase survival rates	Deliver GPX1; reduce oxidative stress; reduce apoptosis	[91]