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Abstract
Background. There is growing interest in new therapeutic options for the treatment of end-stage liver diseases. The use of pluripotent stem cells from human fetuses, umbilical cords, or embryonic tissues derived from in vitro fertilized eggs raises ethical and legal questions, poses a risk of transmitting infections, and/or may be ineffective because of immune rejection. The transplantation of hepatocyte-like cells derived from adult stem cells thus offer great perspectives. Under certain culture conditions, human peripheral blood monocytes were induced to partial repression of hematopoietic markers and reactivation of pluripotency genes with further expression of phenotypic and functional markers of non- haematopoietic lineages. This study evaluated the differentiation potential of terminally differentiated human peripheral blood monocytes into hepatocyte-like cells (NeoHep). Results. NeoHep cells resembled primary human hepatocytes with respect to morphology, expression of hepatocyte markers (albumin, cytochrome P450 3A4 and 2B6 isoenzymes, and coagulation factor VIII), and secretory function (albumin secretion). They were positive for alpha fetoprotein and cytokeratin 18. Conclusions. These data convincingly show that NeoHep cells, which were easily generated from peripheral blood monocytes, display a phenotype and specific in vitro functions. These cells could thus be clinically applied in an autologous setting for the treatment of end-stage liver diseases or for improving liver function in patients who have undergone critical liver-mass resection.