Freeman A E, Engvall E, Hirata K, Yoshida Y, Kottel R H, Hilborn V, Ruoslahti E
Proc Natl Acad Sci U S A. 1981 Jun;78(6):3659-63. doi: 10.1073/pnas.78.6.3659.
Fetal mouse liver hepatocytes proliferate on a substrate of irradiated pigskin epidermis scored with scalpel blade slits to permit cell access to the basement membrane. At the time the cells are explanted, fetal genes, such as those responsible for production of alpha-fetoprotein (AFP) and gamma-glutamyltransferase (GGTase), are strongly expressed. The levels of GGTase decrease rapidly and become undetectable within 2 weeks. The levels of AFP decrease more gradually but become undetectable after 3-5 weeks in culture. As the AFP levels decrease, there is a concomitant increase in albumin production. Hydrocortisone prolongs production of AFP (for up to 8 weeks) but not of GGTase, and it decreases albumin production for up to 8 weeks. Once cells lose AFP expression, addition of hydrocortisone does not restart it. Based on these data, fetal mouse liver hepatocytes, cultured on pigskin, seem to be an excellent in vitro model for liver cell maturation.
将胎鼠肝脏肝细胞接种在经手术刀划痕的辐照猪皮表皮基质上,以便细胞能够接触到基底膜,此时胎鼠肝脏肝细胞会增殖。在细胞被移植时,诸如负责产生甲胎蛋白(AFP)和γ-谷氨酰转移酶(GGTase)的胎儿基因会强烈表达。GGTase的水平迅速下降,在2周内变得无法检测到。AFP的水平下降较为缓慢,但在培养3 - 5周后变得无法检测到。随着AFP水平的下降,白蛋白的产生会相应增加。氢化可的松可延长AFP的产生(长达8周),但对GGTase则无此作用,并且它会使白蛋白的产生减少长达8周。一旦细胞失去AFP表达,添加氢化可的松也无法使其重新表达。基于这些数据,在猪皮上培养的胎鼠肝脏肝细胞似乎是肝细胞成熟的一种极佳体外模型。