In Vitro Functionality of Human Fetal Liver Cells and Clonal Derivatives under Proliferative Conditions

Cell Transplantation

Article

Aniska A. Chhatta¹  Ronald P. J. Oude Elferink¹  Jurgen Seppen¹  Robert A. F. M. Chamuleau¹  Tanja Deurholt¹  Lysbeth Ten Bloemendaal²  Albert C. W. A. Van Wijk²  Ruurdtje Hoekstra²  Kees Weijer³ 

[1] AMC Liver Center, Academic Medical Center, Amsterdam, The Netherlands;AMC Liver Center, Academic Medical Center, Amsterdam, The Netherlands;Department of Surgery (Surgical Laboratory), Academic Medical Center, Amsterdam, The Netherlands;Department of Surgery (Surgical Laboratory), Academic Medical Center, Amsterdam, The Netherlands;

关键词: Hepatocyte;    Fetal;    Proliferation;    Liver function;    In vitro;   

DOI  :  10.3727/000000006783464417

 received in 2005-10-13, accepted in 2006-08-11,  发布年份 2006

来源: Sage Journals

【 摘 要 】

Mature human hepatocytes are not suitable for large-scale in vitro applications that rely on hepatocyte function, due to their limited availability and insufficient proliferation capacity in vitro. In contrast, human fetal liver cells (HFLC) can be easily expanded in vitro. In this study we evaluated the hepatic function of HFLCs under proliferative conditions, to determine whether HFLCs can replace mature hepatocytes for in vitro applications. HFLCs were isolated from fetal livers of 16 weeks gestation. Hepatic functions of HFLCs were determined in primary culture and after expansion in vitro. Clonal derivatives were selected and tested for hepatic functionality. Results were compared to primary mature human hepatocytes in vitro. No differences were observed between primary HFLCs and mature human hepatocytes in albumin production and mRNA levels of various liver-specific genes. Ureagenesis was 4.4-fold lower and ammonia elimination was absent in HFLCs. Expanding HFLCs decreased hepatic functions and increased cell stretching. In contrast, clonal derivatives had stable functionality and morphology and responded to differentiation stimuli. Although their hepatic functions were higher than in passaged HFLCs, functionality was at least 20 times lower compared to mature human hepatocytes. HFLCs cannot replace mature human hepatocytes in in vitro applications requiring extensive in vitro expansion, because this is associated with decreased hepatic functionality. Selecting functional subpopulations can, at least partly, prevent this. In addition, defining conditions that support hepatic differentiation is necessary to obtain HFLC cultures suitable for in vitro hepatic applications.

【 授权许可】

Unknown   
© 2006 Cognizant Comm. Corp.