Transplantation of mesenchymal stem cells for the treatment of liver diseases, is there enough evidence?

Abstract

Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been extensively investigated in small animal models to treat both acute and chronic liver injuries. Mechanisms of action are not clearly elucidated but may include their ability to differentiate into hepatocyte-like cells, to reduce inflammation, and to enhance tissue repair at the site of injury. This approach is controversial and evidence in large animals is missing. Side effects of MSC infusion such as the contribution to a fibrotic process have been reported in experimental settings. Nevertheless, MSCs moved quickly from bench to bedside and over 280 clinical trials are registered, of which 28 focus on the treatment of liver diseases. If no severe side-effects were observed so far, long-term benefits remain uncertain. More preclinical data regarding mechanisms of action, long term safety and efficacy are warranted before initiating large scale clinical application. The proposal of this review is to visit the current state of knowledge regarding mechanisms behind the therapeutic effects of MSCs in the treatment of experimental liver diseases, to address questions about efficacy and risk, and to discuss recent clinical advances involving MSC-based therapies.

hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury

“…MSC transplantation has been investigated in clinical trials as potential treatment for liver diseases, [28][29][30] because systemic injection has been shown to be effective in experimental research. [31][32][33] This therapeutic effect may include transdifferentiation of MSCs into hepatocytelike cells, secretion of anti-inflammatory factors, and hepatocyte regeneration promotion at the site of injury.…”

Methods of Liver Stem Cell Therapy in Rodents as Models of Human Liver Regeneration in Hepatic Failure

“…35 MSC are positive for CD90, CD105 and CD73 and negative for CD45, CD34, CD14, CD11b, CD79a and human leukocyte antigen (HLA)-DR. 36 Fluorescence-activated cell sorting showed gene expression of CD90 and CD29 but not CD45 in MCS from rats. 37 The natural environments of MSC are hypoxic and published data showed hypoxia preconditioning to have supporting effects on the cell survival and genetic instability of these cells, confirming a new insight towards overcoming poor engraftment after transplantation at the bed side.…”

“…21,40 For assessing the differentiation of MSC to liver cells, hepatocytes marker genes such as ALB and α-fetoproteins analysed during in vitro differentiation. 5,37 ESC and MSC are two more common types of stem cells that are used to differentiate to hepatocytes.…”

Mesenchymal Stem Cells and Platelet Derived Concentrates in Regenerative Medicine

“…Mesenchymal stem cells are a significant type of adult stem cells that they can extracted from a variety of tissue ( Figure 1), including adipose tissue [1][2][3][4], skeletal muscle tissue [5], synovial membranes [6], cervical tissue [7], saphenous veins [8], periodontal ligaments [9], Wharton's jelly [10], umbilical cord blood [11], umbilical cords [12], amniotic fluid [13], dental pulp [14], placentae [15], lung tissue [16,17], liver tissue [18,19], and dermal tissue [19].…”