Ehashi Tomo, Ohshima Norio, Miyoshi Hirotoshi
Department of Biomedical Engineering, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
J Biomed Mater Res A. 2006 Apr;77(1):90-6. doi: 10.1002/jbm.a.30631.
A three-dimensional (3-D) culture experiment of porcine fetal liver cells (FLCs) was performed using a porous resin substrate, for the purpose of developing a bioartificial liver. A long-term 3-D culture and monolayer culture as the control were performed for more than 1 month. To promote cell growth and maturation, human oncostatin M (OSM), the human leukemia inhibitory factor (LIF), or cortisol was added to the cultures, and the effect of each agent on cell proliferation and liver-specific cellular functions was investigated. The cell numbers in both the monolayer and 3-D cultures increased gradually with time, irrespective of the supplementation of the stimulating agents. In the monolayer culture, the albumin secretion of FLCs decreased rapidly, and scarce activity was detected from 2 weeks onward under all culture conditions tested. In the 3-D cultures, neither human OSM nor human LIF had any definite effect on the albumin secretion of FLCs. However, in the cultures with cortisol, albumin secretion was maintained for a considerably long period. These findings suggest that a bioartificial liver can be developed by culturing porcine FLCs with cortisol as the stimulant.
为了开发一种生物人工肝,使用多孔树脂基质对猪胎儿肝细胞(FLCs)进行了三维(3-D)培养实验。以长期三维培养和单层培养作为对照,实验持续了1个多月。为促进细胞生长和成熟,向培养物中添加了人制瘤素M(OSM)、人白血病抑制因子(LIF)或皮质醇,并研究了每种试剂对细胞增殖和肝脏特异性细胞功能的影响。无论是否添加刺激剂,单层培养和三维培养中的细胞数量均随时间逐渐增加。在单层培养中,FLCs的白蛋白分泌迅速下降,并且在所有测试培养条件下,从第2周起检测到的活性就很低。在三维培养中,人OSM和人LIF对FLCs的白蛋白分泌均无明确影响。然而,在添加皮质醇的培养物中,白蛋白分泌维持了相当长的时间。这些发现表明,以皮质醇作为刺激剂培养猪FLCs可以开发出生物人工肝。