Immunological basis of stem cell therapy in liver diseases

Abstract

Unbalanced immune cell populations or immune cell infiltration of the liver can disrupt the immune-privileged state of the liver, resulting in liver injury or fibrosis. Therefore, the treatment for liver diseases involves not only hepatic regeneration but also immunological regulation. Recent studies demonstrated that stem cells, especially mesenchymal stem cells, have the capacity for not only hepatic differentiation but also immunomodulation. In this respect, stem cell therapy could be a realistic aim for liver diseases by modulating the liver regenerative processes and down-regulating immune-mediated liver damage. In this review, we discuss in detail the importance of immune cells in liver injury and repair; the mechanism by which stem cells demonstrate an immune-tolerant phenotype that can be used for allogeneic transplantation; the effect of stem cell transplantation on immune-mediated diseases, especially liver diseases; and the mechanism by which stem cells improve the hepatic microenvironment.

Keywords::

• hepatic microenvironment
• immunology
• liver disease
• stem cell therapy
• stem cells

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The liver is enriched in immune cells including hepatic macrophages, natural killer T cells, T cells and B cells. An unbalanced immune cell population or immune cell infiltration in the liver can disrupt the immune-privileged state of the liver, resulting in liver injury or fibrosis. Immune cell-based therapy for liver fibrosis can improve fibrosis, regeneration and function.

• Stem cells can renew themselves as well as transform into hepatocyte-like cells in vitro and in vivo. Moreover, stem cells, especially mesenchymal stem cells, possess an immune-tolerant phenotype, which allows them be used for allogenic treatments; stem cells also have immunosuppressive or immunomodulatory abilities, which allow for their use in immune-mediated disease treatment.

• Liver injury is caused by persistent inflammation, which is accompanied by T cell, B cell and monocyte infiltration of the liver. Stem cell therapy could be a realistic aim for liver diseases to improve regeneration and reduce scarring in liver cirrhosis by modulating the liver’s own regenerative processes and also downregulating immune-mediated liver damage.

• Stem cells can be safely used to treat immune-mediated diseases including nonautoimmune-mediated liver disease and autoimmune liver disease. Stem cell therapy can prolong patient survival times by reducing the occurrence of complications and improving liver function. Their beneficial action on liver diseases, at least partly, occurs through regulating the hepatic microenvironment.

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