Co-culture system of hepatocytes and endothelial cells: two in vitro approaches for enhancing liver-specific functions of hepatocytes
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Although hepatocyte transplantation and bioartificial liver support system provide new promising opportunities for those patients waiting for liver transplantation, hepatocytes are easily losing liver-specific functions by using the common in vitro cultured methods. The co-culture strategies with mimicking the in vivo microenvironment would facilitate the maintenance of liver-specific functions of hepatocytes. Considering that hepatocytes and endothelial cells (ECs) account for 80–90% of total cell populations in the liver, hepatocytes and ECs were directly co-cultured with hepatic stellate cells (HSCs) or adipose tissue-derived stem cells (ADSCs) at a ratio of 700:150:3 or 14:3:3 in the present study, and the liver-specific functions were carefully analyzed. Our results showed that the two co-culture systems presented the enhanced liver-specific functions through promoting secretion of urea and ALB and increasing the expressions of ALB, CYP3A4 and HNF4α, and the vessel-like structure in the co-culture system consisted of hepatocytes, ECs and ADSCs. Hence, our results suggested that the directly co-culture of hepatocytes and ECs with HSCs or ADSCs could significantly improve liver-specific functions of hepatocytes, and the co-culture system could further promote angiogenesis of ECs at a later stage. Therefore, this study provides potential interesting in vitro strategies for enhancing liver-specific functions of hepatocytes.
KeywordsCo-culture system Hepatocytes Endothelial cells Adipose tissue-derived stem cells Liver Hepatic stellate cells
This work was supported by the National Natural Science Foundation of China (Grant No. 81472830); the Natural Science Foundation of Fujian (Grant No. 2017J01266); the Science and Technology Infrastructure Construction Program of Fujian Province (Grant No. 2014Y2005); the Youth Scientific Research Project of Fujian Provincial Health and Family Planning Commission (Grant No. 2017-1-85); the Startup Fund for scientific research, Fujian Medical University (Grant No. 2016QH081); the Project of Fuzhou Science and Technology Department (Grant Nos. 2016-s-124-9 and 2016-s-124-4); the Scientific Foundation of Fuzhou Health Department (Grant No. 2015-S-wq13); and the Project of Quanzhou Science and Technology Department (Grant No. Z  0098).
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Conflict of interest
The authors declare that they have no conflict of interest.
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