The effectiveness of a novel cartridge-based bioreactor design in supporting liver cells.
The effectiveness of a novel cartridge-based bioreactor design in supporting liver cells.
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基于盒的新型生物反应器设计在支持肝细胞方面的有效性。
DOI：
10.1089/ten.tea.2008.0279
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发表时间：
2009
影响因子：
--
通讯作者：
Coger,RobinN
中科院分区：
文献类型：
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作者：
Niu,Mei;Hammond2nd,Paul;Coger,RobinN
有许多应用——从器官衰竭的临时策略到药物测试——都依赖于有效的生物反应器设计。这些装置的意义在于，它们提供了一个维持细胞的环境，使它们能够执行关键的细胞和组织功能。本研究开发并评价了一种新型的筒状生物反应器。其独特的特点包括细胞支持能力和细胞空间的适应性设计。具体来说，它能够容纳功能和合理大小的组织（>2.0 × 108细胞），并且可以很容易地修改以支持一系列锚定依赖性细胞。为了评价其疗效，本研究将其应用于肝支持。这包括评估大鼠原代肝细胞在无生物反应器培养的独特培养皿中的表现，以及在装入新型生物反应器后的表现。与胶原夹心培养功能对照相比，在独特设计的培养皿中，肝细胞在动态流动条件下的白蛋白产量和尿素分泌率显著提高，峰值分别为170±22 μg/106cells/day和195±18 μg/106cells/day。生物反应器在支持活的和功能的原代肝细胞方面的有效性也被提出。在新的生物反应器中培养15天后，细胞存活率为84±18%，表明新的设计可以有效地维持原代肝细胞至少2周的培养。还评估了尿素分泌、白蛋白合成和细胞色素P450活性的肝脏特异性功能。结果表明，在新型生物反应器中培养的肝细胞能够获得良好的功能性能。在细胞色素P450活性的情况下尤其如此，在培养的第15天，生物反应器中的肝细胞达到了比胶原三明治功能对照培养高56.6%的值。新型生物反应器在支持具有良好活力和功能性能的肝细胞方面的成功表明，它是一种支持锚定依赖性细胞的有效设计。
There are a number of applications—ranging from temporary strategies for organ failure to pharmaceutical testing—that rely on effective bioreactor designs. The significance of these devices is that they provide an environment for maintaining cells in a way that allows them to perform key cellular and tissue functions. In the current study, a novel cartridge-based bioreactor was developed and evaluated. Its unique features include its capacity for cell support and the adaptable design of its cellular space. Specifically, it is able to accommodate functional and reasonably sized tissue (>2.0 × 108cells), and can be easily modified to support a range of anchorage-dependent cells. To evaluate its efficacy, it was applied to liver support in the current study. This involved evaluating the performance of rat primary hepatocytes within the unique cartridges in culture—sans bioreactor—and after being loaded within the novel bioreactor. Compared to collagen sandwich culture functional controls, hepatocytes within the unique cartridge design demonstrated significantly higher albumin production and urea secretion rates when cultured under dynamic flow conditions—reaching peak values of 170 ± 22 μg/106cells/day and 195 ± 18 μg/106cells/day, respectively. The bioreactor's effectiveness in supporting live and functioning primary hepatocytes is also presented. Cell viability at the end of 15 days of culture in the new bioreactor was 84 ± 18%, suggesting that the new design is effective in maintaining primary hepatocytes for at least 2 weeks in culture. Liver-specific functions of urea secretion, albumin synthesis, and cytochrome P450 activity were also assessed. The results indicate that hepatocytes are able to achieve good functional performance when cultured within the novel bioreactor. This is especially true in the case of cytochrome P450 activity, where by day 15 of culture, hepatocytes within the bioreactor reached values that were 56.6% higher than achieved by the collagen sandwich functional control cultures. The success of the novel cartridge-based bioreactor in supporting hepatocytes with good viability and functional performance suggests that it is an effective design for supporting anchorage-dependent cells.