5 research outputs found

    Bioartificial livers in vitro and in vivo: tailoring biocomponents to the expanding variety of applications

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    Bioartificial livers (BALs) were originally developed to treat patients suffering from severe liver failure and relied on primary hepatocytes or on hepatoblastoma-derived cell lines. Currently, new in vitro BAL applications are emerging, including drug toxicity testing, disease modeling and basic clinical research, and in recent years, advances in the field of stem cell biology have resulted in potential alternative cell sources. This review identifies the demands of clinical and in vitro BAL applications to their biocomponent and summarizes the functionality and developmental state of BAL technology and cell types currently available. Relevant studies identified by searching the MEDLINE database until April 2014 were reviewed, supplemented with some of our own unpublished data. BALs have the potential to meet demands currently left unmet in both clinical and in vitro applications. All the reviewed biocomponents show limitations towards one or more BAL applications. However, the generation of stem cell-derived hepatocyte-like cells is progressing rapidly, so the criteria for patient-specific drug toxicity screening and disease modeling are probably met in the near future. HepaRG cells are the most promising biocomponent for clinical BAL application, based on their proliferative and differentiation capacit

    Formation of the ether lipids archaetidylglycerol and archaetidylethanolamine in Escherichia coli

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    In archaea, the membrane phospholipids consist of isoprenoid hydrocarbon chains that are ether-linked to a sn-glycerol 1-phosphate backbone. This unique structure is believed to be vital for the adaptation of these micro-organisms to extreme environments, but it also reflects an evolutionary marker that distinguishes archaea from bacteria and eukaryotes. CDP-archaeol is the central precursor for polar head group attachment. We examined various bacterial enzymes involved in the attachment of L-serine and glycerol as polar head groups for their promiscuity in recognizing CDP-archaeol as a substrate. Using a combination of mutated bacterial and archaeal enzymes, archaetidylethanolamine (AE) and archaetidylglycerol (AG) could be produced in vitro using nine purified enzymes while starting from simple building blocks. The ether lipid pathway constituted by a set of archaeal and bacterial enzymes was introduced into Escherichia coli, which resulted in the biosynthesis of AE and AG. This is a further step in the reprogramming of E. coli for ether lipid biosynthesis.</p
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