Co-culture system of hepatocytes and endothelial cells: two in vitro approaches for enhancing liver-specific functions of hepatocytes |
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Authors: | Gaoxiong Wang Youshi Zheng Yingchao Wang Zhixiong Cai Naishun Liao Jingfeng Liu Wenmin Zhang |
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Affiliation: | 1.Department of Hepatobiliary Surgery,The Second Affiliated Hospital of Fujian Medical University,Quanzhou,People’s Republic of China;2.The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou,People’s Republic of China;3.The Liver Center of Fujian Province,Fujian Medical University,Fuzhou,People’s Republic of China;4.Liver Disease Center,The First Affiliated Hospital of Fujian Medical University,Fuzhou,People’s Republic of China;5.Department of Pathology,Fujian Medical University,Fuzhou,People’s Republic of China |
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Abstract: | 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. |
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