Topic Highlight
Copyright ©The Author(s) 2016.
World J Gastroenterol. Jan 7, 2016; 22(1): 24-36
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.24
Table 1 Proposed cellular and molecular mechanisms that could contribute to hepatic protection by mesenchymal stem cells in alcoholic liver disease
MSCs in liver inflammation
Inhibit the proliferation of CD8 cytotoxic T lymphocytes and increase the relative rate of CD4 Th2 lymphocytes[97,100]
Inhibit the maturation of monocytes into dendritic cells[94]
Inhibit the secretion of TNF-α, INF-γ, and IL-12 by dendritic cells and increase their secretion of IL-10, reducing the proinflammatory potential[95]
Suppress the proliferation, cytolytic activity, and cytokine secretions of the NK cells[96]
Express indoleamine 2,3-dioxygenase upon INF-γ stimulation, leading to tryptophan depletion and the inhibition of T-cell proliferation[98]
MSCs in liver fibrosis
Reduce the proliferation of HSCs and the synthesis of collagen type I through the secretion of TNF-α[125]
Induce HSCs apoptosis[124]
Express matrix metalloproteinase-9, which degrades the extracellular matrix[128,129]
MSCs in liver regeneration
Secrete trophic factors (HGF, EGF, and IGF-1) that promote hepatocyte proliferation and function during liver regeneration[68,128,130]
Table 2 Preclinical studies using mesenchymal stem cells or their derivatives to treat liver injury
Model animal speciesLiver injury induction/kind of liver injuryMSCs administration routeNumber andsource of transplanted MSCsTherapeutic effectProposed mechanismsRef.
RatAllyl alcohol (ip administration)/chronic damageIntrahepatic1 × 106 MSCs from human BMHepatocyte regenerationHepatocyte differentiation without evidence of cell fusion[76]
MouseLow-level of radiation/minimal, hepatic damageTail vein2 × 104 MSCs from mouse BMHepatocyte regenerationHepatocyte differentiation[78]
MouseChronic exposure to high fat diet/NASHTail vein0.5 × 106 MSCs from mouse BMPrevention of NASH onsetParacrine promotion of hepatic proliferation[110]
Preclusion of the inflammatory processIncrease in the fatty-acid oxidation enzymes expression
MouseChronic exposure to atherogenic diet/NASHSplenic capsule0.1 × 106 MSCs from mouse adipose tissueRestoration of albumin expression in hepatic parenchymal cellsModulation of inflammation[111]
Amelioration of fibrosisIncrease in MMP expression
Suppression of persistent hepatic inflammation
MouseCCl4 (ip administration)/liver fibrosisSpleen0.5 × 106 MSCs from human amniotic membraneReduction of liver fibrosisInactivation of HSCs[126]
Improvement of hepatic functionReduction of hepatocyte apoptosis
Promotion of liver regeneration
Differentiation of hepatocyte-like cells
MouseCCl4 (ip administration)/liver fibrosisTail vein0.5 × 106 MSCs from human BMReduction of liver fibrosisInduction of MMP-9 expression[121]
Reduction in TGF-β expression
RatD-galactosamine (ip administration)/fulminant hepatic failurePenile veinConditioned medium from human BM MSCsReduction in the mortality rateModulation of the immune response[105,122]
Reduction in panlobular leukocyte infiltratesTrophic factor release (i.e., VEGF, HGF, and IGF-BP)
Reduction in hepatocellular death
MouseCCl4 (ip administration)/liver fibrosisIntrahepaticExosomes derived from human umbilical cord MSCsRecovery of serum aspartate aminotransferase activityNot determined[109]
Decrease in collagen type I and III, TGF-β1 level