Mesenchymal-Epithelial Transition in Culture of Stromal Progenitor Cells Isolated from the Liver of a Patient with Alcoholic Cirrhosis

Abstract

The cells isolated from biopsy specimen of a patient with alcoholic liver cirrhosis and cultured under standard conditions for obtaining stromal cell culture clearly diverged during early passages into two morphologically and phenotypically different subtypes: epithelial and mesenchymal. Mesenchymal cells expressed CD90 and CD44 and epithelial cells expressed CD166, CD227, and hepatocyte growth factor receptor Met. Starting from passage 6, the culture underwent spontaneous morphological changes and by passages 8-10 contained only epithelium-like cells. CD90 and CD44 expression disappeared, CD166 and CD227 expression remained unchanged, and Met expression increased. A small fraction of cells expressed GATA-4, HNF3β, HNF1α, and HNF4α. After addition of inducers of hepatogeneic differentiation, the cells started producing albumin.

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

“…We [29], as well as other authors [30,31], obtained liver MSCs from liver biopsy material by tissue disintegration and subsequent processing with collagenase. The resulting cell suspension, without any additional manipulations, was placed in uncoated culture flasks and incubated in the medium for the cultivation of MSCs (DMEM + 10–20% FBS).…”

“…Our gene expression microarray data show that MSCs isolated from the liver of patients with fibrosis or cirrhosis express several liver-specific genes: ribonuclease RNase A family 4 ( RNASE4 ), CYP1A2 , γ-glutamyl transpeptidase ( GGT1 ), and glutamine synthase ( GLUL )—at a low level; CYP1B1 —at a relatively high level; a very high level of expression was observed only for the NNMT gene encoding the nicotinamide N -methyltransferase. Albumin, α-phetoprotein ( AFP ), and hepatocyte nuclear factor-4 ( HNF4A ) were not expressed in our liver MSCs both at the protein level [29] and at the mRNA level. At the same time, expression of the c-Met hepatocyte growth factor receptor was detected by us in 60% of cells in the liver MSC population by flow cytometry [29] as well as at the transcriptome level (see Table 1).…”

“…Albumin, α-phetoprotein ( AFP ), and hepatocyte nuclear factor-4 ( HNF4A ) were not expressed in our liver MSCs both at the protein level [29] and at the mRNA level. At the same time, expression of the c-Met hepatocyte growth factor receptor was detected by us in 60% of cells in the liver MSC population by flow cytometry [29] as well as at the transcriptome level (see Table 1).…”

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

“…It should be noted, that there are discrepancies in the data presented by authors in the literature concerning the pattern of markers expressed by epithelial and mesenchymal afterbirth cells [109,181]. Native human afterbirth cells share some phenotypic features comparable with human hepatic multipotent stem cells (hHpSC) and bipotent hepatoblasts: EpCAM, CK19, CD133 [17,27,35,181], adult multipotent stem cells expressing mesenchymal markers: CD44, CD73, CD90, CD105, CK19, SSEA-4, NANOG, OCT-4 [15,52,66,67,181,[53][54][55][56][57][58][59][60] and adult bipotent hepatic progenitor cells (HPC): DLK-1 [78,184]. EpCAM expression, characteristic of hepatoblasts, but not of mesenchymal liver cells, has been confirmed in afterbirth cells only in few studies [181,[183][184][185].…”

Markers for the Characterization of Liver Mesenchymal Stem Cell

“…Jones et al [24] reported that bovine BMSCs are positive for expression of CD166. In addition, bovine LMSCs are negative for expression of CD166 but positive for expression of CD44, CD29, CD73, CD90, and CD106 [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. +( 32)…”