OXYGEN IS A FACTOR DETERMINING IN-VITRO TISSUE ASSEMBLY - EFFECTS ON ATTACHMENT AND SPREADING OF HEPATOCYTES

OXYGEN IS A FACTOR DETERMINING IN-VITRO TISSUE ASSEMBLY - EFFECTS ON ATTACHMENT AND SPREADING OF HEPATOCYTES
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DOI:
10.1002/bit.260430715
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发表时间:
1994-03-25
影响因子:
3.8
通讯作者:
YARMUSH, ML
YARMUSH, ML
中科院分区:
工程技术2区
文献类型:
--
作者:
ROTEM, A;TONER, M;YARMUSH, ML

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最近许多与生物人工肝装置发展相关的研究都利用了在各种几何形状的装置中培养的肝细胞。由于肝细胞是锚定依赖细胞,它们需要附着并扩散到细胞外基质上才能发挥作用,这一过程需要能量。因此,在细胞组织的早期阶段,当细胞与细胞外基质相互作用时,向含有生物人工肝装置的肝细胞提供足够的氧气是很重要的。在这项研究中,我们研究了氧对肝细胞附着和扩散的影响。将气相氧从0增加到160 mmHg,在接种1 h后,细胞附着率从43.0 +/- 5.8%增加到103.6 +/- 29%。同样,在播种后24小时,将气相氧从0增加到160 mmHn,导致预计表面积从310 +/- 35增加到827 +/- 127 mu m(2)。此外,用扩散反应模型估计了细胞水平上的氧分压。该模型表明,细胞表面氧分压为0.064 mmHg时,肝细胞与胶原基底物的附着达到半最大(K-m(a))。另一方面,预测扩散过程的K-m(s)值为0.13 mmHg。本研究结果证明了氧在肝细胞附着和扩散的初始阶段的重要性,这对基于肝细胞的生物人工肝装置的设计具有重要意义。(C) 1994 John wiley & Sons, Inc。
Many recent studies related to the development of bioartificial liver devices have utilized hepatocytes cultured within devices of various geometries. Because hepatocytes are anchorage-dependent cells, they need to attach and spread onto the extracellular matrix to be able to function, a process that requires energy. Thus, it is important to deliver enough oxygen to hepatocytes contained within bioartificial liver devices during the early phase of cellular organization while the cells interact with the extracellular matrix. In this study, we investigated the effect of oxygen on the attachment and spreading of hepatocytes. Increasing the gas phase oxygen from 0 to 160 mmHg resulted in an increase in the percentage of cells attaching from 43.0 +/- 5.8% to 103.6 +/- 29%, 1 h after seeding. In a similar manner, increasing the gas phase oxygen from 0 to 160 mmHn resulted in an Increase of the projected surface area from 310 +/- 35 to 827 +/- 127 mu m(2), 24 h after seeding. Furthermore, the partial pressure of oxygen at the cell level was estimated using a diffusion-reaction model. The model indicated that a cell surface oxygen partial pressure of 0.064 mmHg was required for the half-maximal (K-m(a)) attachment of hepatocytes to collagen-based substrate. On the other hand, the K-m(s) value of the spreading process was predicted to be 0.13 mmHg. The results of this study demonstrate the importance of oxygen during the initial stages of attachment and spreading of hepatocytes, and it has important implications in the design of hepatocytebased bioartificial liver devices. (C) 1994 John wiley & Sons, Inc.