The hepatic differentiation of adult and fetal liver stromal cells in vitro

Abstract

The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells. However, to improve the effectiveness of such treatment it is necessary to search for more optimal sources of progenitor cells, as well as to evaluate the possibility of using descendants of these cells differentiated in vitro. In this study we isolated stromal cells from the liver biopsies of three patients with alcoholic cirrhosis, conducted their morphological and phenotypic analysis, and evaluated the hepatic potential of these cells in vitro. The stromal cells isolated from fetal liver were used for comparison. The results of this can serve as a basis for the development of a new method for the treatment of end-stage liver disease. The stromal cells isolated from the liver biopsies for a long time proliferate in a culture and this which makes it possible to expand them to large amounts for subsequent differentiation into hepatocyte-like cells and autologous transplantation.

Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

“…For example, Najimi et al [20] found that 99% of liver MSCs were positive for CD90, 92% of the cells were positive for CD73, 88% were positive for CD29, 92% for CD44, and 76% for HLA-Class I. In our work, we showed by flow cytometry that only about 30% of liver MSCs isolated from the liver of patients with cirrhosis and fibrosis expressed CD90 and CD44 [33]. Moreover, a gene expression microarray confirmed that the expression level of CD90 ( THY1 ) was low, while the expression level of CD44 was very high (our unpublished data; see Table 1).…”

“…As with MSCs isolated from other sources, liver MSCs do not express markers of hematopoietic and endothelial cells, such as CD11b, CD14, CD19, CD31, CD34, CD45, CD79β, CD117, CD133, CD144, and HLA-DR [20,23,27,33,36]. The lack of expression of CD34, CD45, and CD117 on the surface of liver MSCs suggests that these cells are not so-called hepatic progenitor cells (the human counterpart to rodent oval cells) which are bipotent resident hepatic cells that can differentiate into hepatocytes and cholangiocytes [28,38].…”

“…Several research groups using different differentiation protocols (Table 3) have demonstrated the ability of human liver MSCs to differentiate into hepatocyte-like cells in vitro [20,21,27,33,34,72,94]. The opposite was reported in just one paper by Porretti et al [92] claiming that cultured CD105 + CD73 + Thy-1 + CD45 − CD34 − MSCs obtained from the mononuclear fraction of the liver after removal of hepatocytes did not differentiate into the endothelial and hepatic lineages.…”

The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress

“…The unique features of these cells include immunomodulatory properties and extensive regenerative potential. As shown by several research groups, the liver contains a pool of resident MSCs, which, in terms of their main characteristics (expression patterns of cell surface markers, adhesion, and morphology), correspond to those of MSCs isolated from other tissue sources [12][13][14]. Liver MSCs have several unique characteristics compared with those obtained from other tissue sources.…”