Table 2 Representative studies using MSCs in experimental models of liver injury and their therapeutic mechanisms
Animal models | Source of MSCs | Doses of MSCs | Route of administration | Representative biological activities | Refs. |
|---|---|---|---|---|---|
APAP-induced acute liver failure in mice | Human umbilical MSCs | 1.0 × 106 | Intravenous (tail vein) | Attenuate hepatocyte necrosis by secreting hepatocyte growth factor and MDSC infiltration | [11] |
TAA-injured rat model | Human PD-MSCs | 2.0 × 106 | Intravenous (tail vein) | Trigger the regeneration of organ (e.g., liver and ovary) damaged by oxidative stress from TAA treatment via activating antioxidant factors | [16] |
DGaIN-induced acute liver failure in rats | Rat bone marrow MSCs | 5.5 × 105 | Intravenous (tail vein) | Induce M2 macrophage polarization by activating STAT6; increase the expression of anti-inflammatory factors to alleviate ALF | [24] |
LPS/D-Gal-induced acute liver failure in mice | Mouse bone marrow MSCs | 2.0 × 106 | Intravenous (tail vein) | Inhibit liver inflammatory response and hepatocyte death | [28] |
CCl4-induced liver fibrosis in mice | Human umbilical MSCs | 1.0 × 106 | Intravenous (tail vein) | Alleviate liver fibrosis and modulate macrophage phenotype to regulate inflammatory microenvironment in liver and repair the injury | [30] |
CCl4-induced acute liver injury in mice | Mouse bone marrow MSCs | 5.0 × 105 | Intravenous (tail vein) | Alleviate ALI and mitigate the recruitment of mononuclear phagocytes; attenuate the recruitment of neutrophils by reducing the expression of CXCL2 of MoMF | [31] |
Ethanol-induced liver injury | Mouse bone marrow MSCs | 5.0 × 106 | Intraperitoneal (i.p.) | Inhibit hepatic neutrophil and macrophage infiltration and alleviate oxidative stress | [35] |
Ethanol-induced liver injury | Human umbilical MSCs | 1.0 × 106 repeated injection | Intravenous intraperitoneal | Improve survival and recovery of hepatic chemistries | [37] |
Con A-induced liver injury in mice | Human umbilical MSCs | 1.0 × 106 | Intravenous (tail vein) | Suppress T cell activation and production of pro-inflammatory cytokines through CHI3L1 | [49] |
TAA-induced fibrosis in mice | Human ASCs | N/A | Intravenous (tail vein) | Reduce collagen content in the liver; inhibit proinflammatory cytokines; reduce elevated liver enzymes | [59] |
DDC-induced liver injury | Human MenSCs | 5.0 × 105 | Intravenous (tail vein) | Repair the DDC-induced liver injury; inhibit COL1A1, α-SMA and TGF-β1 activation by upregulating liver β-catenin expression | [63] |
CCl4-induced liver fibrosis in mice | Human umbilical MSCs | N/A | – | Induce ferroptosis of HSCs by regulating the xCT/GPX4 axis and alleviate liver fibrosis | [68] |
CCl4-induced ACLF in mice | Human bone marrow MSCs | N/A | Intravenous (tail vein) | Restore the impaired autophagic flux and alleviate liver injury | [80] |
MCD-induced NASH in mice | Human umbilical MSCs | N/A | Intravenous (tail vein) | Regulate the anti-inflammatory phenotype of macrophages and reverse PPAR-α protein expression in liver cells | [84] |
T2DM-associated NAFLD in mice | Mouse bone marrow MSCs | 1.0 × 107 cells/kg body weight | Intravenous (tail vein) | Recover increasing weight, HFD-induced steatosis, liver function, and disordered glucose and lipid metabolism via rescuing dysfunction mitochondria | [87] |
S. japonicum-induced schistosomiasis in mice | Human umbilical MSCs | N/A | Intravenous (tail vein) | Downregulate HSCs activation and reduce liver injury | [96] |
IRI in rats | Human umbilical MSCs | 3.0 × 106; N/A | Intravenous (tail vein) | Alleviate hepatic ischemia–reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response | [101] |