Table 4.

Experimental liver fibrosis and bone marrow mesenchymal stem cells.

Cells/Dose/Route	Fibrosis Model	Main Results and Mechanisms of Action	Reference
Mouse BMMSC and CM-BMMSC, 106 cells	CCl4 (intraperitoneal) in C57BL/6 mice, 1 µL/g, 2x per week, 1 month	IDO promoted Th17 suppression (IL-17 reduction) and IL-10 production and activation of CD4 T cells.	[115]
Human BMMSC and EX-BMMSC, 106 cells	CCl4 (intraperitoneal) in Sprague Dawley rats	EX-BMMSC had better therapeutic effect; IL-1, IL-2, IL-6, IL-8, and TNF-α reduction; PPARγ, Wnt3a, Wnt10b, β-catenin, WISP1, Cyclin D1 were decreased; inhibition of hepatic stellate cell activation	[118]
Mouse BMMSC and HNF-4α-overexpressing BMMSC, 106 cells	CCl4 (intragastric gavage) in C57BL/6 mice, 5.0 mL/kg, 2x per week, 3 weeks	HNF-4α-overexpressing BMMSC had better therapeutic effect; reduction in TNF-α, IFN-γ, IL-6; enhanced iNOS expression that depends on NF-κB signalling; Kupffer cell inhibition	[119]
Rat BMMSC, 3 × 106 cells	CCl4 (intraperitoneal) in Sprague Dawley rats, 1 mL/g, 2x per week, 6 weeks	Reduction in IL-17, IL-2 and IL-6; downregulation of IL-17a, IL-17ra, IL-17f, Stat3, p-STAT3, Stat5a, p-SMAD3, and TGFβR2; elevation of p-STAT5 protein	[114]
Rat BMMSC, HGF overexpressing BMMSC and HGF alone	CCl4 (intraperitoneal) in Sprague Dawley rats, 5.0 mL/kg, 30 consecutive days	AST, ALT, total bilirubin levels reduction; hepatocyte nuclear factor 4α, albumin, and cytokeratin 18 expression were increased	[120]
Mouse BMMSC, 5 × 105 cells	CCl4 (intraperitoneal) in C57BL/6 mice, 1 mL/g, 70 days	IL-10 increase and IL-12b, IFN-γ, TNF-α, and IL-6 gene expression were decreased; M2 macrophages activation; MMP13 production and M1 macrophages inhibition	[117]
Rat BMMSC, 106 cells	Bile duct ligation in Sprague Dawley rats	T cell proliferation was decreased; inflammatory cytokines were reduced; expansion of intrahepatic NK cells	[116]
Rat BMMSC, 106 cells or Silymarin (100 mg/kg)	Bile duct ligation in Wistar rats	BMMSC had a better therapeutic effect; MMP-2 mRNA upregulation and CK-19 mRNA downregulation; HGF augmentation regulate MMP-2 and CK-19 gene expression	[121]
Human BMMSC, HGF-overexpressing BMMSC, 4 × 106 cells	CCl4 (intraperitoneal) in Sprague Dawley rats, 0.2 mL/100 mg, 3x per week, 8 weeks	HGF overexpressing BMMSC had better therapeutic effect; HGF overexpressing increased homing of BMMSC in the liver	[122]
Human BMMSC, HGF-overexpressing BMMSC, 107 cells	Dimethylnitrosamine (intraperitoneal) in Sprague Dawley rats, 1 mL/g, three consecutive days per week, 4 weeks	HGF overexpressing BMMSC had better therapeutic effect; reduction in PDGF-bb, TGF-β1, and TIMP2; inhibition of α-SMA cells	[123]