Liver tissue engineering: A role for co-culture systems in modifying hepatocyte function and viability

Liver tissue engineering: A role for co-culture systems in modifying hepatocyte function and viability
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DOI:
10.1089/10763270152044206
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发表时间:
2001-06-01
期刊:
影响因子:
--
通讯作者:
Shakesheff, KM
Shakesheff, KM
中科院分区:
生物2区
文献类型:
--
作者:
Bhandari, RNB;Riccalton, LA;Shakesheff, KM

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构建功能性工程化肝脏的主要限制是培养中肝细胞的短期存活和快速去分化。异型细胞-细胞相互作用可能在调节工程组织中的长期肝细胞行为中发挥作用。我们描述了3 T3成纤维细胞在共培养系统中调节原代分离大鼠肝细胞功能和活力的潜力。在分离后的18天内,纯培养的肝细胞活力迅速下降,显示稀疏的胆小管,并失去了两个功能标志物,白蛋白和乙氧基试卤灵O-脱烷基酶(EROD)活性的分泌。相比之下,共培养物中的肝细胞保持活力,具有良好形成的小管系统,并显示两种功能标志物。固定的3 T3细胞或3 T3细胞条件培养基不能替代活的3 T3细胞共培养系统以保持肝细胞活力和功能。
A major limitation in the construction of a functional engineered liver is the short-term survival and rapid de-differentiation of hepatocytes in culture. Heterotypic cell-cell interactions may have a role to play in modulating long-term hepatocyte behavior in engineered tissues. We describe the potential of 3T3 fibroblast cells in a co-culture system to modulate function and viability of primary isolated rat hepatocytes. Over an 18-day period after isolation, hepatocytes in pure culture rapidly declined in viability, displayed sparse bile canaliculi, and lost two function markers, the secretion of albumin and ethoxyresorufin O-dealkylase (EROD) activity. In comparison, the hepatocytes within the co-cultures maintained viability, possessed well-formed canalicular systems, and displayed both functional markers. Fixed 3T3 cells or 3T3 cell conditioned medium did not substitute for the viable 3T3 cell co-culture system in preserving hepatocyte viability and functionality.