Hepatic maturation of human fetal hepatocytes in four-compartment 3D perfusion culture. Tissue engineering. Part C, Methods [Tissue Eng Part C Methods] Journal article | | Title | Hepatic maturation of human fetal hepatocytes in four-compartment 3D perfusion culture. | | Author(s) | Ring A, Gerlach JC, Peters G, Pazin B, Minervini C, Turner ME, Thompson RL, Triolo F, Gridelli B, Miki T | | Institution | Charité, Campus Virchow-Clinic, Department of Surgery, Berlin, Germany; alexander.ring@charite.de. | | Source | Tissue Eng Part C Methods 2009 Nov 2. | | Abstract | Bio-artificial liver support systems have been utilized as bridging devices to support acute and chronic liver injury. However, prolonged function of adult hepatocytes has not been achieved due to compromised proliferation and long-term survival of adult cells in vitro. As an alternative cell source, we investigated the potential of human fetal hepatocytes in a four-compartment hollow fiber based three-dimensional (3D) perfusion culture system. Human fetal hepatocytes were isolated from 17-19 gestational week livers and cultured in the 3D-perfusion bioreactors for 14 days. Metabolism activity, hepatocyte-specific gene expression, protein expression, and hepatic function were investigated. Increased glucose consumption and lactate production indicated cell proliferation in the bioreactor. The ratio of cytochrome P450 3A4 to 3A7 gene expression and the increase of the number of asialoglycoprotein receptor positive cells indicated cell differentiation into mature hepatocytes. Histological and immunohistochemical analysis revealed reorganization of fetal liver cells. Hepatic function was further examined for ammonia metabolism and for albumin production using colorimetric assays and ELISA, respectively. In contrast with conventional 2D culture, the 3D-perfusion culture system induced functional maturation to human fetal hepatocytes; these cells may be useful as an alternative cell source for extracorporeal liver support. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19883207 |
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