Mesenchymal stem cell therapies for liver cirrhosis: MSCs as “conducting cells” for improvement of liver fibrosis and regeneration

Abstract

Mesenchymal stem cells (MSCs) can be cultured relatively easily and can be obtained not only from the bone marrow, but also from medical waste such as adipose tissue and umbilical cord tissue. Because of its low antigenicity, allogeneic MSC injection is safe. MSCs have been evaluated in more than 900 clinical trials in a variety of fields, with more than 50 clinical trials related to liver diseases. Experiments have suggested that MSCs function as “conducting cells” to affect various “effective cells” such as T cells, B cells, and macrophages. Recent clinical trials have focused on allogeneic MSCs. Thus, studies are needed to determine the most effective cell source, culture conditions, cell numbers, administration frequency, administration route, cost, safety, and liver disease treatments. Recently, the functions of exosomes have gained attention, and cell-free therapy may become possible as an alternative therapy for liver disease. In this review, we introduce general information, mechanism, representative clinical study data, recently started or planned clinical trials, and possibility of cell-free therapy of MSCs.

Antifibrotic Effect of Combination of Nilotinib and Stem Cell-Conditioned Media on CCl4-Induced Liver Fibrosis

“…The antifibrotic effect of the combination of Nilotinib and stem cell-conditioned media may be due to a synergistic effect of the two types of treatment ( Figure 5). Mesenchymal stem cell-conditioned media have anti-inflammatory effects and reduce damages to hepatocytes which stop the activation of hepatic stellate cells (HSC) leading to apoptosis of HSC and fibrinolysis activation [11]. Alternatively, MSCs change the polarity of macrophages towards an antiinflammatory phenotype, increase the production of matrix metalloproteinases to reduce the ECM, and increase the ability of phagocytosis of hepatocyte debris (during this process, macrophages increase the levels of proregenerative factors) [29].…”

“…Extracellular vesicles which are secreted by cells are generally defined as microvesicles, cell-derived vesicles, microparticles, shedding vesicles, and exosomes [10]. Exosomes are lipid vesicles which contain evolutionarily conserved sets of proteins including tetraspanins (CD81, CD63, and CD9), heat shock proteins (HSP60, HSP70, and HSP90), and tumor susceptibility gene 101 and have been reported to have multiple functions including angiogenesis, cell proliferation, and collagen reduction [11].…”

Regenerative effect of mesenteric fat stem cells on ccl4-induced liver cirrhosis, an experimental study

“…These studies are very attractive for developing effective anti-cirrhotic therapies. Researches are needed to determine the most valuable cell source, culture condition, cell number, administration frequency, and administration route, at low cost for treating liver diseases [ 28 ]; Also to generalize the results to other species or experimental conditions.…”

Regenerative Effect of Mesenteric Fat Stem Cells on ccl4-Induced Liver Cirrhosis

“…These studies are very attractive for developing effective anti-cirrhotic therapies. Researches are needed to determine the most valuable cell source, culture condition, cell number, administration frequency, and administration route, at low cost for treating liver diseases (28).…”