Injured hepatocyte-released microvesicles induce bone marrow-derived mononuclear cells differentiation

Abstract

The ability of bone marrow-derived mononuclear cells (BMMCs) to differentiate into hepatocyte-like cells under different conditions has been demonstrated previously. In the present study, we investigated the effect of CCl4-injured hepatocytes on the differentiation of the non-adherent (NAD) fraction of BMMCs. Differentiation (cell fate) was analyzed after 2, 6 and 24h of co-culture by gene and protein expression and by urea production. We also evaluated the presence of microvesicles (MVs) in the supernatant of differentiated cells, their content and the ability of these cells to absorb them. Hepatocyte-like characteristics were observed in the NAD cells after 24h of co-culture with injured hepatocytes. Cells that were co-cultured with healthy hepatocytes did not present signs of differentiation at any analyzed time point. Analysis of the supernatant from differentiated cells revealed the presence of MVs carrying hepatocyte-specific mRNAs, including Albumin, Coagulation factor V, Alpha-fetoprotein, and Cytokeratin 18. The incorporation of injured hepatocyte-derived MVs by NAD cells was shown at 24h, suggesting a possible role for MVs in the induction of cell plasticity.