Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis

Abstract

Liver fibrosis is a common feature of chronic liver disease. Activated hepatic stellate cells (HSCs) are the main drivers of extracellular matrix accumulation in liver fibrosis. Hence, a strategy for regulating HSC activation is crucial in treating liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from various post-natal organs. Therapeutic approaches involving MSCs have been studied extensively in various diseases, including liver disease. MSCs modulate hepatic inflammation and fibrosis and/or differentiate into hepatocytes by interacting directly with immune cells, HSCs, and hepatocytes and secreting modulators, thereby contributing to reduced liver fibrosis. Cell-free therapy including MSC-released secretomes and extracellular vesicles has elicited extensive attention because they could overcome MSC transplantation limitations. Herein, we provide basic information on hepatic fibrogenesis and the therapeutic potential of MSCs. We also review findings presenting the effects of MSC itself and MSC-based cell-free treatments in liver fibrosis, focusing on HSC activation. Growing evidence supports the anti-fibrotic function of either MSC itself or MSC modulators, although the mechanism underpinning their effects on liver fibrosis has not been established. Further studies are required to investigate the detailed mechanism explaining their functions to expand MSC therapies using the cell itself and cell-free treatments for liver fibrosis.

ECM1 modified HF-MSCs targeting HSC attenuate liver cirrhosis by inhibiting the TGF-β/Smad signaling pathway

“…On the other hand, MSCs can exert indirect effects on HSCs by acting on immune cells, the immune response was reduced due to the immunosuppressive properties of MSCs, thereby reducing the pro-fibrotic stimulation of immune cells to HSCs [ 46 ]. It is widely accepted that the MSCs anti-fibrotic effect is mainly due to the paracrine factors [ 47 , 48 ], the specific mechanism of HF-MSCs on HSCs deserves further exploration.…”

Mesenchymal stromal cells (MSCs) and their exosome in acute liver failure (ALF): a comprehensive review

“…The indirect secretion of some pivotal factors (IL-10, HGF, TGF-β, and TNF-α) by MSCs averts the growth of HSCs and reduces the formation of collagen. In contrast, HGF and NGF enhance the apoptosis of HSCs [ 88 , 89 ].…”

Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy

“…In liver spread of colon, pancreatic, and breast cancers, the presence and activation of resident stellate cells is important in preparing a microenvironment that propagates metastatic seeding [ 54 ] and growth [ 55 , 56 , 57 , 58 ]. The ability of stellate cell activation to influence metastatic growth is reported to involve their ability to influence fibrosis and ECM deposition/stiffness [ 58 , 59 , 60 ]. It will be interesting to confirm how the liver microenvironment actually responds to PCa.…”