Stem cell transplantation for treatment of liver diseases: From biological foundations to clinical experience (Review)

The insufficiency of liver functions remains one of the major causes of death in different regions of the world. This syndrome is an ultimate outcome of irreversible damage of liver parenchyma by a variety of stimuli such as environmental toxins and microbial metabolites. The acute and/or chronic inflammation caused by these agents leads to massive apoptosis of hepatocytes, highly specialized polyfunctional epithelial cells. A decrease in the number of hepatocytes below the critical level dictates the necessity of supplanting the exogenous viable cells. Such cells must fulfill two major requirements: i) they should be capable of proliferating in the recipient's liver, and ii) they should differentiate into mature (i.e, functionally competent) hepatocytes. Evidence is growing in support of the role of early pluripotent precursors (stem cells of various origin) as a unique source for transplantation. This review analyses the state-of-the-art in the fields of developmental biology, cytology, molecular physiology and biochemistry of fetal stem cells with the emphasis on their use in experimental models of liver insufficiency. These biological considerations validate the therapeutic manipulations with fetal cells in clinical trials.