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. 2021 Nov 2;9(11):1598. doi: 10.3390/biomedicines9111598

Table 3.

Summary of MSC cell-free therapy for liver fibrosis.

Type Treatment Target/Experimental Model Mechanism Outcome Ref
In vitro MSC-CM HSCs Reducing expressions of
pro-fibrotic genes		 Inhibition of
HSCs activation		 [131]
Cytokine, TSG-6 HSCs Decreasing HSC activation
Promoting the transdifferentiation of activated HSCs into
stem-like cells		 Amelioration of
liver fibrosis		 [136]
MSC-exosomes HSCs Inhibiting Wnt/β-catenin signaling Inhibition of
HSC activation		 [144]
Co-culture with
miR-125b manipulated MSCs		 LX2 Targeting Smo;
suppression of Hh signaling		 Inhibition of
HSC activation		 [149]
In vivo MSC-CM CCl4-induced liver fibrosis in mice Reducing collagen accumulation and inflammation
Elevating hepatocyte survival		 Amelioration of
liver fibrosis		 [132]
Cytokine, TSG-6 CCl4-induced liver fibrosis in mice Inducing M2 polarization
Upregulating MMP12 expression in macrophages		 Amelioration of
liver fibrosis		 [137]
Cytokine, MFGE 8 TAA or CCl4-induced liver fibrosis in mice Downregulating the expression of TGFβR1 of HSC Amelioration of
liver fibrosis		 [138]
MSC-exosomes CCl4-induced liver fibrosis in mice Reducing hepatocyte death
Decreasing oxidative stress		 Amelioration of
liver fibrosis		 [142]
CCl4-induced liver fibrosis in mice Inactivating TGF-β/SMAD
signaling pathway		 Amelioration of
liver fibrosis		 [143]
CCl4-induced liver fibrosis in rats Suppressing Wnt/β-catenin
signaling		 Improvement of
liver function		 [144]
GPX1 delivered by the MSC-exosomes CCl4-induced liver fibrosis in mice Decreasing oxidative stress
Increasing hepatocyte proliferation		 Amelioration of
liver fibrosis		 [145]
miR-150-5p contained in MSC-exosomes CCl4-induced liver fibrosis in mice Reducing the expression of
CXCL-1		 Amelioration of
liver fibrosis		 [14]
miR-1246 contained in MSC-exosomes ischemia/reperfusion-induced liver injury in mice Modulating the balance of
regulatory T cells and Th17 cells		 Protection of hepatocytes Suppression of inflammation [147]
miR-486-5p contained in MSC-exosomes CCl4-induced liver fibrosis in mice Suppressing Hh signaling Amelioration of
liver fibrosis		 [148,149]
miR-125b contained in MSC-exosomes CCl4-induced liver fibrosis in rats

MSC, Mesenchymal stem cell; HSC, Hepatic stellate cell; CM, Conditioned media; TSG-6, Tumor necrosis factor-inducible gene 6 protein; miR, MicroRNA; Hh, Hedgehog; Smo, Smoothened; MMP12, Matrix metalloproteinase 12; MFGE8, Milk fat globule EGF factor 8 protein; CCl4, Carbon tetrachloride; TAA, Thioacetamide; TGFβR1, Transforming growth factor beta-receptor 1; TGF-β, Transforming growth factor beta; GPX1, Glutathione peroxidase 1; Th17, T helper 17; CXCL-1, CXC chemokine-ligand-1.