David Bertrand, Dufresne Murielle, Nagel Marie-Danielle, Legallais Cécile
CNRS Unit UMR 6600 Biomechanics and Biomedical Engineering, Technological University of Compiègne, BP 20529, 60205 Compiègne Cedex, France.
Biotechnol Prog. 2004 Jul-Aug;20(4):1204-12. doi: 10.1021/bp034301z.
In the present in vitro model, the authors intended to assess viability and functionality of hepatocytes encapsulated into alginate beads and submitted to a fluidized bed motion in a bioreactor. Human immortalized C3A line was chosen as cell model. Two controls consisting of (1) cells cultured on flasks and (2) cells encapsulated in alginate beads under static conditions were implemented. The cell functions studied were total protein, albumin, urea, and ammonia synthesis, as well as ammonia removal in the case of overdose. The comparison among the three cases studied showed that the three-dimensional structure of alginate offered a suitable environment for cell functions. In addition, the fluidized bed bioreactor enhanced the mass transfer and thus increased the amount of species released out of the beads, as compared with the static case. Ammonia detoxification only appeared reduced by encapsulation. The concept of a fluidized bed bioartificial liver was thus validated by this in vitro model, which indicated that cell functions could be efficiently retained. In addition, as far as urea and protein synthesis and release were concerned, the use of the C3A cell line, in combination with encapsulation and fluidization technology, offered a real potentiality for the purpose of extracorporeal liver supply.
在当前的体外模型中,作者旨在评估封装在藻酸盐珠粒中并在生物反应器中进行流化床运动的肝细胞的活力和功能。选择人永生化C3A细胞系作为细胞模型。实施了两个对照组,分别为:(1)在培养瓶中培养的细胞;(2)在静态条件下封装在藻酸盐珠粒中的细胞。所研究的细胞功能包括总蛋白、白蛋白、尿素和氨的合成,以及过量情况下的氨去除。对所研究的三种情况进行比较表明,藻酸盐的三维结构为细胞功能提供了适宜的环境。此外,与静态情况相比,流化床生物反应器增强了传质,从而增加了从珠粒中释放出的物质的量。仅通过封装,氨解毒作用似乎有所降低。因此,这种体外模型验证了流化床生物人工肝的概念,表明细胞功能能够有效地保留。此外,就尿素和蛋白质的合成及释放而言,将C3A细胞系与封装和流化技术相结合,为体外肝脏供应提供了真正的潜力。