Stem cell therapies for autoimmune hepatitis

Abstract

Autoimmune hepatitis is a chronic inflammatory hepatic disorder which may cause liver fibrosis. Appropriate treatment of autoimmune hepatitis is therefore important. Adult stem cells have been investigated as therapies for a variety of disorders in latest years. Hematopoietic stem cells (HSCs) were the first known adult stem cells (ASCs) and can give rise to all of the cell types in the blood and immune system. Originally, HSC transplantation was served as a therapy for hematological malignancies, but more recently researchers have found the treatment to have positive effects in autoimmune diseases such as multiple sclerosis. Mesenchymal stem cells (MSCs) are ASCs which can be extracted from different tissues, such as bone marrow, adipose tissue, umbilical cord, and dental pulp. MSCs interact with several immune response pathways either by direct cell-to-cell interactions or by the secretion of soluble factors. These characteristics make MSCs potentially valuable as a therapy for autoimmune diseases. Both ASC and ASC-derived exosomes have been investigated as a therapy for autoimmune hepatitis. This review aims to summarize studies focused on the effects of ASCs and their products on autoimmune hepatitis.

Keywords: Autoimmune hepatitis; Exosomes; Hematopoietic stem cells; Mesenchymal stem cell; Mesenchymal stromal cell; Stem cells.

Fig. 1

Postulated immunomodulatory role of MSCs, modified MSCs, and their exosomes in an AIH animal model. AIH, autoimmune hepatitis; Th17, T helper 17 cells; IL, interleukin; CTL, cytotoxic CD8+ T lymphocyte; JAK, Janus kinase; STAT, signal transducer and activator of transcription; FASL, Fas ligand; IFN-γ, interferon-gamma; PD-L1, the ligand of PD-1 “programmed death-1”; TNF, tumor necrosis factor; NLRP3, nucleotide-binding domain-like receptor protein 3. The figure was created using the images from Servier Medical Art