Autoregulation of Hepatic Macrophage Activation in Sepsis

Effect of cell–cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells

“…Hepatocyte viability and liver‐specific function have been shown to be stabilized for several weeks in vitro upon cocultivation with a variety of other cell types. The resultant cocultures have been widely used in studies of various physiological and pathophysiologic processes including host response to sepsis (23, 24), mutagenesis (25–28), xenobiotic toxicity (29, 30), response to oxidative stress (31), lipid metabolism (32, 33), and induction of the acute‐phase response (34–37). In addition, the ability to preserve key features of the hepatocyte phenotype in vitro may have important applications in hepatocyte‐based therapies for liver disease.…”

“…Table 1 summarizes studies of both liver and non-liver-derived cell types in hepatocyte cocultures. Liver-derived cell types include rat liver epithelial cells of presumed biliary origin (31, 37, 39 -46), stellate (Ito, fat-storing) cells (47)(48)(49), sinusoidal endothelial cells (50,51), Kupffer cells (24,(52)(53)(54)(55)(56), and the entire 'nonparenchymal' fraction of isolated liver cells (57)(58)(59). Although this effect on morphological and functional differentiation was originally thought to be species specific, many other cell types from other organ systems and species have since been shown to influence isolated rat hepatocytes.…”

“…The glutathione-S-transferase (GST) family, a family of dimeric enzymes that catalyze the conjugation of reduced glutathiones to electrophiles, is the most commonly studied of the phase II systems. Like the Rat liver epithelial (presumed biliary origin) (31, 37, 39, 40-42, 44-46, 59) Bovine aortic endothelia (51, 66) Stellate (47)(48)(49) Canine kidney epithelia (65) Sinusoidal endothelial (50,51) Chinese hamster epithelia (25, 28) Kupffer (24,(52)(53)(54)(55)(56) Embryonic murine (3T3, C3H 10T 1 2 ) (29,32,45,51,60,(63)(64)(65) 'Nonparenchymal' fraction of isolated population (57)(58)(59) Human fibroblast (26,27,67,68) Human lung epithelia (65) Human venous endothelia (42) Monkey kidney epithelia (65,78) Rat dermal fibroblast (51) cytochrome P-450 isoenzymes, GSTs are generally more stable in coculture than pure hepatocyte culture (31, 43-46, 83, 84). Stable expression of some subunits has been noted for 12 days in coculture, with significant quantitative differences between various nonparenchymal cell sources (44,78).…”

Bioengineered Liver Models for Drug Testing and Cell Differentiation Studies

“…In vitro, co-culture with both liver- and non–liver-derived NPC types can transiently induce functions in primary hepatocytes from multiple species, including human beings. 37 Although the complete mechanism underlying this so-called co-culture effect remains undefined, liver co-cultures have proven useful for investigating host response to sepsis, 38 mutagenesis, 39 xenobiotic metabolism and toxicity, 40 response to oxidative stress, 41 lipid metabolism, 42 and induction of the acute phase response 43 ; such co-cultures also have been explored for clinical bioartificial liver devices. 44 However, randomly distributed co-cultures do not allow precise modulation of homotypic and heterotypic cell–cell interactions that play critical roles in liver functions.…”

Πρωτογενείς Καλλιέργειες Ανθρωπίνων Κυττάρων Ήπατος

“…Ως στηρικτικοί μη παρεγχυματικοί πληθυσμοί χρησιμοποιούνται συχνότερα κύτταρα ήπατος, όπως επιθηλιακά κύτταρα αρουραίων χολαγγειακής προέλευσης 21 ,. αστεροειδή κύτταρα ενδοθηλιακά κύτταρα κολποειδών22 , και κύτταρα Kupffer23 Εκτός από τα κύτταρα του ήπατος έχουν πραγματοποιηθεί καλλιέργειες ηπατοκυττάρων και με κύτταρα από άλλους ιστούς όπως ενδοθηλιακά κύτταρα αορτής24 , κύτταρα νεφρικού επιθηλίου από σκύλο25 εμβρυικά κύτταρα ποντικού 3Τ326 ,ανθρώπινοι ινοβλάστες 27 ,ανθρώπινο πνευμονικό επιθήλιο και πολλοί άλλοι συνδυασμοί. είναι ορατές μόνο εφόσον η συγκαλλιέργεια ξεκινά όχι αργότερα από την 3 η ως την 7 η ημέρα 32.…”