title: Autologous serum improves yield and metabolic capacity of monocyte-derived hepatocyte-like cells: possible implication for cell transplantation.
abstract: Hepatocyte-transplantation is a therapeutic approach for diverse acute and chronic liver diseases. As availability of primary cells is limited, there is an increasing demand for hepatocyte-like cells (e.g., neohepatocytes generated from peripheral blood monocytes). The aim of this study  was to evaluate the effects of six different human AB sera, fetal calf serum, or autologous serum on production of neohepatocytes. The yield and quality of neohepatocytes varied considerably depending on the different sera. Using autologous sera for the whole production process we constantly  generated the highest amount of cells with the highest metabolic activity for phase I (e.g., CYP1A1/2, CYP3A4) and phase II enzymes (e.g., glutathione-S-transferase). Moreover, similar effects were seen examining glucose and urea metabolism. Especially, glucose-6-phosphatase and PAS  staining showed distinct serum-dependent differences. The role of macrophage activation was investigated by measuring the secretion of TNF-α, TGF-β, and RANKL, MMP activity, as well as mRNA levels of different interleukins in programmable cells of monocytic origin (PCMO). Our data  clearly demonstrate that the use of autologous serum reduced initial macrophage activation in PCMOs and subsequently improved both yield and function of differentiated neohepatocytes. The autologous approach presented here might also be useful in other stem cell preparation processes where  cell activation during generation shall be kept to a minimum.
authors.affiliation: Department of Traumatology, MRI, Technische Universität München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ehnert
authors.forename: C
authors.initials: C
authors.lastname: Seeliger
authors.forename: H
authors.initials: H
authors.lastname: Vester
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.forename: S
authors.initials: S
authors.lastname: Saidy-Rad
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: M
authors.initials: M
authors.lastname: Neumaier
authors.forename: S
authors.initials: S
authors.lastname: Gillen
authors.forename: J
authors.initials: J
authors.lastname: Kleeff
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: J
authors.initials: J
authors.lastname: Burkhart
authors.forename: U
authors.initials: U
authors.lastname: Stöckle
authors.forename: A K
authors.initials: AK
authors.lastname: Nüssler
mesh_terms: D000643:Ammonium Chloride / Q000378:metabolism; D017690:Cell Transplantation; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation; D020782:Matrix Metalloproteinases / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D009000:Monocytes / Q000166:cytology*; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014508:Urea / Q000378:metabolism
chemical_list: D007378:Interleukins; D053245:RANK Ligand; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000643:Ammonium Chloride; D014508:Urea; D020782:Matrix Metalloproteinases; D005947:Glucose