Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment

Abstract

Hepatic fibrosis/cirrhosis is a significant health burden worldwide, resulting in liver failure or hepatocellular carcinoma (HCC) and accounting for many deaths each year. The pathogenesis of hepatic fibrosis/cirrhosis is very complex, which makes treatment challenging. Endogenous mesenchymal stromal cells (MSCs) have been shown to play pivotal roles in the pathogenesis of hepatic fibrosis. Paradoxically, exogenous MSCs have also been used in clinical trials for liver cirrhosis, and their effectiveness has been observed in most completed clinical trials. There are still many issues to be resolved to promote the use of MSCs in the clinic in the future. In this review, we will examine the controversial role of MSCs in the pathogenesis and treatment of hepatic fibrosis/cirrhosis. We also investigated the clinical trials involving MSCs in liver cirrhosis, summarized the parameters that need to be standardized, and discussed how to promote the use of MSCs from a clinical perspective.

Keywords: Clinical application; Hepatic fibrosis/cirrhosis; Mesenchymal stromal cells; Pathogenesis; Treatment.

Fig. 1

The role of MSCs in hepatic fibrosis formation and therapy. A In the process of chronic inflammatory injury of liver, the synergistic effect from inflammation and the death of hepatocytes promotes the formation of hepatic fibrosis. B The mechanisms of MSC therapy in hepatic fibrosis, including hepatic differentiation, hepatocyte protection, inhibition of HSC activation, ECM degradation and inflammation inhibition

Fig. 2

Clinical trials of MSCs in liver diseases. A An overall of clinical trials based on MSCs classified by liver disease type. B Clinical trials of liver cirrhosis based on MSCs classified by the clinical phase. C Clinical trials of liver cirrhosis based on MSCs classified by status. The data showed the number and percentage

Fig. 3

The parameters need to be standardized precisely in clinical application of MSCs in liver cirrhosis. Currently, MSCs used in clinical trials for liver cirrhosis treatment are obtained from different sources (bone marrow, umbilical cord, adipose tissue and menstrual blood). During the process of MSC preparation, there are various imprecise parameters, including donor seleciton, isolation methods, culture conditions, cryopreservation and thaw and cell heterogeneity. MSCs are transferred at different dosages and through different routes. All of the above parameters would affect the therapeutic effect of MSCs and disturbing a best standard for clinical application of MSCs is essential for the successful clinical translation of MSCs in the future

Fig. 4

Clinical trials of liver cirrhosis based on MSCs application. A Clinical trials of liver cirrhosis based on different sources of MSCs. B Clinical trials of liver cirrhosis based on autologous and allogeneic transplantation of MSCs. C Clinical trials of liver cirrhosis based on transplantation routes of MSCs. The data showed the No. and percentage of corresponding clinical trials