Tilles A W, Baskaran H, Roy P, Yarmush M L, Toner M
Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, MA 92114, USA.
Biotechnol Bioeng. 2001 Jun 5;73(5):379-89. doi: 10.1002/bit.1071.
The goal of this study was to investigate the viability and synthetic function of rat hepatocytes cocultured with 3T3-J2 fibroblasts in a small-scale microchannel flat-plate bioreactor with and without an internal membrane oxygenator under flow. Bioreactor channel heights ranged between 85 and 500 microm and medium flow rates ranged between 0.06 and 4.18 mL/min. The results showed that the bioreactor without the oxygenator resulted in significantly decreased viability and function of hepatocytes, whereas hepatocytes in the bioreactor with internal membrane oxygenator were able to maintain their viability and function. The shear stress calculations showed that, at lower wall shear stresses (0.01 to 0.33 dyn/cm(2)), hepatocyte functions, measured as albumin and urea synthesis rates, were as much as 2.6- and 1.9-fold greater, respectively, than those at higher wall shear stresses (5 to 21 dyn/cm(2)). Stable albumin and urea synthesis rates for 10 days of perfusion were also demonstrated in the bioreactor with internal membrane oxygenator. These results are relevant in the design of hepatocyte bioreactors and the eventual scaling-up to clinical devices.
本研究的目的是在有或无内置膜式氧合器的小型微通道平板生物反应器中，在流动条件下研究与3T3-J2成纤维细胞共培养的大鼠肝细胞的活力和合成功能。生物反应器通道高度在85至500微米之间，培养基流速在0.06至4.18毫升/分钟之间。结果表明，没有氧合器的生物反应器导致肝细胞活力和功能显著下降，而带有内置膜式氧合器的生物反应器中的肝细胞能够维持其活力和功能。剪切应力计算表明，在较低壁面剪切应力（0.01至0.33达因/平方厘米）下，以白蛋白和尿素合成率衡量的肝细胞功能分别比在较高壁面剪切应力（5至21达因/平方厘米）下高2.6倍和1.9倍。在带有内置膜式氧合器的生物反应器中也证明了灌注10天期间白蛋白和尿素合成率稳定。这些结果与肝细胞生物反应器的设计以及最终扩大到临床设备相关。
