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

Table 1.

Summary of MSC administration for liver fibrosis.

Type Treatment Target/Experimental Model Mechanism Outcome Ref
In vitro Direct contact
with MSCs		 HSCs Upregulating Notch1 expression
Downregulating PI3K/Akt pathway		 Suppression of HSC proliferation [71]
Co-culture with MSCs HSCs Upregulating p27kip1 and p21cip1
Downregulating cyclin D and p-ERK		 [72]
Co-culture with MSCs HSCs Increasing pro-apoptotic proteins
(Bax and cleaved caspase-3)		 Increase of apoptosis of activated HSCs [73]
Co-culture with MSCs HSCs Secreting NGF; inhibition of NF-κB
Decrease of Bcl-xl expression		 [74]
Direct contact or co-culture with MSCs LX2 Releasing HGF; inhibition of NF-κB [75]
Co-culture with MSCs KCs Promoting secretion of anti-inflammatory cytokines Alleviation of
immune response		 [82]
Co-culture with MSCs NK cells Producing PGE2; impairment of proliferation and activation of NK cells [89]
Hepatocyte differentiating factors Hepatocytes Inducing expression of hepatocyte markers
(albumin, α-fetoprotein)		 Differentiation of MSCs into functional hepatocytes [63,92,93,94,95]
In vivo MSC transplantation CCl4-induced
liver fibrosis in rats		 Inhibiting proliferation and promoting apoptosis of activated HSCs Amelioration of
liver fibrosis		 [76]
MSC transplantation DMN-induced
liver fibrosis in rats		 Releasing IL-4 and IL-10 Alleviation of
immune response and liver fibrosis		 [82]
MSC transplantation CCl4-induced
liver fibrosis in mice		 Decreasing IL-17
Increasing IL-10		 [86]
MSC transplantation CCl4-induced
liver fibrosis in mice		 Increasing IDO level and decreasing IL-17; decrease of proliferation of Th17 cells [91]
MSCs derived hepatocyte-like cells transplantation CCl4-induced
liver fibrosis in mice		 Mimicking hepatocyte functions Amelioration of
liver fibrosis
Improvement of
liver function		 [96]

MSC, Mesenchymal stem cell; HSC, Hepatic stellate cell; HGF, Hepatocyte growth factor; NF-κB, Nuclear factor kappa B; Bcl-xl, B cell leukemia-xl; KC, Kupffer cell; IL, Interleukin; Th17, T helper 17; NK, Natural killer; CCl4, Carbon tetrachloride; DMN, Dimethylnitrosamine; PGE2, prostaglandin E2; IDO, Indoleamine 2,3-dioxygenase.