Primary or Established Liver Cells for a Hybrid Liver?

Stange, Jan; Mitzner, Steffen; Strauss, Margaret B.; Fischer, Ute; Lindemann, Stephen R.; Peters, E; Holtz, M.; Drewelow, Bernd; Schmidt, R.

doi:10.1097/00002480-199507000-00020

Cited by 21 publications

(9 citation statements)

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“…This data shows that C3A cells have a similar phenotype to the parental HepG2 cell line as regards urea cycle expression (Mavri-Damelin et al, 2007). However, C3A cells are cited in the literature as being able to produce urea, and whilst this has been assumed to be reflective of a functional urea cycle (David et al, 2004;Ellis et al, 1996;Filippi et al, 2004;Stange et al, 1995;Wang et al, 1998), we have conclusively shown by stable isotope labelling, that ammonia cannot be specifically removed by this pathway and converted to urea. This has significant implications in the development and use of C3A cells in BAL devices, where they are currently used and considered to possess urea cycle function and therefore ammonia detoxificatory capability (Ellis et al, 1996); of course this study did not address their potential value in liver failure via provision of the other synthetic and detoxificatory functions that they possess.…”

Section: Discussionmentioning

confidence: 75%

Cells for bioartificial liver devices: The human hepatoma‐derived cell line C3A produces urea but does not detoxify ammonia

Mavri-Damelin

Damelin

Eaton³

et al. 2007

Biotech & Bioengineering

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Extrahepatic bioartificial liver devices should provide an intact urea cycle to detoxify ammonia. The C3A cell line, a subclone of the hepatoma-derived HepG2 cell line, is currently used in this context as it produces urea, and this has been assumed to be reflective of ammonia detoxification via a functional urea cycle. However, based on our previous findings of perturbed urea-cycle function in the non-urea producing HepG2 cell line, we hypothesized that the urea produced by C3A cells was via a urea cycle-independent mechanism, namely, due to arginase II activity, and therefore would not detoxify ammonia. Urea was quantified using (15)N-ammonium chloride metabolic labelling with gas chromatography-mass spectrometry. Gene expression was determined by real-time reverse transcriptase-PCR, protein expression by western blotting, and functional activities with radiolabelling enzyme assays. Arginase inhibition studies used N(omega)-hydroxy-nor-L-arginine. Urea was detected in C3A conditioned medium; however, (15)N-ammonium chloride-labelling indicated that (15)N-ammonia was not incorporated into (15)N-labelled urea. Further, gene expression of two urea cycle genes, ornithine transcarbamylase and arginase I, were completely absent. In contrast, arginase II mRNA and protein was expressed at high levels in C3A cells and was inhibited by N(omega)-hydroxy-nor-L-arginine, which prevented urea production, thereby indicating a urea cycle-independent pathway. The urea cycle is non-functional in C3A cells, and their urea production is solely due to the presence of arginase II, which therefore cannot provide ammonia detoxification in a bioartificial liver system. This emphasizes the continued requirement for developing a component capable of a full repertoire of liver function.

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Section: Discussionmentioning

confidence: 75%

Cells for bioartificial liver devices: The human hepatoma‐derived cell line C3A produces urea but does not detoxify ammonia

Mavri-Damelin

Damelin

Eaton³

et al. 2007

Biotech & Bioengineering

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“…The dominating limitation of all cell-based concepts today appears to be the cell source. The use of primary human liver cells is increasingly favored for clinical application, because these cells circumvent several unwanted effects associated with the use of porcine cells (metabolic incompatibility, risk of xenozoonosis) (4-6) or tumor cell lines (risk of metastases and a lower biochemical performance) (7). Discarded donor organs might serve as a source for the isolation of primary human hepatocytes.…”

mentioning

confidence: 99%

Artificial and bioartificial support systems for liver failure

Liu

Gluud

Als‐Nielsen

et al. 2004

Cochrane Database of Systematic Reviews

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“…A major problem for all bioartificial concepts, however, appears to be the cell source: the use of primary human liver cells is increasingly favored for clinical application, because these cells circumvent several unwanted effects associated with the use of porcine cells (metabolic incompatibility, risk for xenozoonosis) (19), or tumor cell lines (risk of metastases and a lower biochemical performance) (20). Discarded donor organs may serve as a source for the isolation of primary human hepatocytes.…”

Section: Liver Support (Ims)mentioning

confidence: 99%