, Volume 70, Issue 4, pp 1279–1290 | Cite as

Co-culture system of hepatocytes and endothelial cells: two in vitro approaches for enhancing liver-specific functions of hepatocytes

  • Gaoxiong Wang
  • Youshi Zheng
  • Yingchao Wang
  • Zhixiong Cai
  • Naishun LiaoEmail author
  • Jingfeng Liu
  • Wenmin ZhangEmail author
Original Article


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.


Co-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 [2014] 0098).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hepatobiliary SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouPeople’s Republic of China
  2. 2.The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouPeople’s Republic of China
  3. 3.The Liver Center of Fujian ProvinceFujian Medical UniversityFuzhouPeople’s Republic of China
  4. 4.Liver Disease CenterThe First Affiliated Hospital of Fujian Medical UniversityFuzhouPeople’s Republic of China
  5. 5.Department of PathologyFujian Medical UniversityFuzhouPeople’s Republic of China

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