INTRODUCTION: Mesenchymal stem/stromal cells (MSCs) improve the metabolic function of co-cultured hepatocytes. The present study aimed to further enhance the trophic effects of co-culture with hepatocytes using @entity519 preconditioning (HPc) of the MSCs and also to investigate the underlying molecular mechanisms involved. METHODS: @entity1 adipose tissue-derived MSCs were subjected to @entity519 (2 % O2; HPc) or normoxia (20 % O2) for 24 h and then co-cultured with isolated @entity1 hepatocytes. Assays of metabolic function and apoptosis were performed to investigate the hepatotrophic and anti-apoptotic effects of co-culture. Indirect co-cultures and co-culture with MSC-conditioned medium investigated the role of paracrine factors in the hepatotrophic effects of co-culture. Reactive @entity26 species (ROS) activity was antagonised with @entity898 to investigate whether HPc potentiated the effects of MSCs by intracellular ROS-dependent mechanisms. Tumour @entity39 factor ( @entity310 , transforming growth factor (TGF)-b1, and extracellular collagen production was determined and @entity8187 and @entity589 / @entity588 signalling pathways analysed to investigate the role of soluble factors, extracellular matrix deposition, and apoptosis-associated gene signalling in the effects of co-culture. RESULTS: HPc potentiated the hepatotrophic and anti-apoptotic effects of co-culture by ROS-dependent mechanisms. There was increased MSC @entity2533 production, and enhanced MSC deposition of extracellular collagen, with reduced synthesis of @entity310 , as well as a downregulation of the expression of pro-apoptotic @entity8187 , @entity589 , @entity5353 and @entity39159 genes and upregulated expression of anti-apoptotic @entity588 in hepatocytes. CONCLUSIONS: HPc potentiated the trophic and anti-apoptotic effects of MSCs on hepatocytes via mechanisms including intracellular ROS, autocrine TGF-b, extracellular collagen and caspase and @entity589 / @entity588 signalling pathways.

XXXX preconditioning potentiates the trophic effects of mesenchymal stem cells on co-cultured @entity1 primary hepatocytes.

@entity1 :: ('9606', 'Species') :: ['human', 'Human'] @entity589 :: ('581', 'Gene') :: ['BAX'] @entity588 :: ('596', 'Gene') :: ['BCL-2'] @entity39159 :: ('640', 'Gene') :: ['BLK'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity310 :: ('7124', 'Gene') :: ['TNF)-a', 'TNF-a'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity898 :: ('MESH:D000111', 'Chemical') :: ['N-acetylcysteine'] @entity8187 :: ('842', 'Gene') :: ['CASP9'] @entity5353 :: ('637', 'Gene') :: ['BID'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxic', 'hypoxia'] @entity2533 :: ('7040', 'Gene') :: ['TGF-b1']
@entity519 :: (MESH:D000860,Disease) :: ['Hypoxic']
