Ehashi Tomo, Koyama Toshie, Ookawa Keiko, 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. 2007 Jul;82(1):73-9. doi: 10.1002/jbm.a.31027.
Vascular endothelial growth factor (VEGF) is crucial for the development and regeneration of the liver. However, there have been no reports about VEGF secretion by cultured fetal liver cells (FLCs). In the present study, the effects of oncostatin M (OSM), which strongly stimulates the growth and albumin secretion of FLCs, on VEGF secretion and morphological changes of long-term cultured FLCs were investigated under three-dimensional (3-D) and monolayer conditions. The cultured FLCs proliferated well and showed stable secretion of VEGF for up to 1 month under both monolayer and 3-D culture conditions. The addition of OSM to cultured cells strongly enhanced VEGF secretion. Compared with 3-D cultures, VEGF secretion per cell was higher in monolayer cultures. After 1 month in culture, the FLCs in 3-D cultures formed large aggregates like liver tissue, and FLCs also formed colonies and duct-like structures after several months of culture even under monolayer conditions. In conclusion, OSM stimulated the secretion of VEGF by cultured FLCs, which seemed to contribute to the development of a liver-like structure.
血管内皮生长因子(VEGF)对肝脏的发育和再生至关重要。然而,关于培养的胎肝细胞(FLCs)分泌VEGF的报道尚未见诸文献。在本研究中,我们在三维(3-D)和单层培养条件下,研究了对FLCs的生长和白蛋白分泌有强烈刺激作用的制瘤素M(OSM),对长期培养的FLCs的VEGF分泌及形态变化的影响。在单层和3-D培养条件下,培养的FLCs增殖良好,并在长达1个月的时间内表现出稳定的VEGF分泌。向培养细胞中添加OSM可强烈增强VEGF分泌。与3-D培养相比,单层培养中每个细胞的VEGF分泌更高。培养1个月后,3-D培养中的FLCs形成了类似肝组织的大聚集体,即使在单层培养条件下,FLCs在培养数月后也形成了集落和管状结构。总之,OSM刺激了培养的FLCs分泌VEGF这似乎有助于类肝结构的形成。