Department of Internal Medicine, University of Turin , San Giovanni Battista Molinette Hospital,Turin, Italy.
Tissue Eng Part C Methods. 2010 Feb;16(1):123-32. doi: 10.1089/ten.TEC.2008.0634.
The use of bioartificial livers (BALs) for the expansion of human adult liver stem cells and the production of growth factors could be a potential strategy for cell-based extracorporeal liver support. The present study aimed to assessing the differentiation of human adult liver stem cells in a rotary BAL. Liver stem cells were seeded into a polysulphone membrane filter at a density of 3 x 10(8) cells, and the filter was connected to a rotary bioreactor perfusion system (37 degrees C, 50 mL/min, 48 h). Viability, cell differentiation, and metabolic performances were evaluated at 24 and 48 h. Hepatocyte growth factor production from human adult liver stem cells, mature hepatocytes, and mesenchymal stem cells in adhesion and in the rotary BAL conditions was compared. Liver stem cells cultured in the rotary BAL produced the highest amounts of albumin (p = 0.002) and ammonia-induced urea (p = 0.0001), and had an increased cytochrome P450 expression in respect to liver stem cells in adhesion. Remarkably, liver stem cells in the rotary BAL produced very high amounts of hepatocyte growth factor (p = 0.005) in respect to hepatocytes and mesenchymal stem cells. Moreover, the cells lost their stem cell markers and acquired several markers of mature hepatocytes. In conclusion, the rotary BAL favored liver stem cell differentiation into mature hepatocyte-like cells.
生物人工肝脏（BAL）可用于扩增人类成体肝干细胞并产生生长因子，这可能成为一种基于细胞的体外肝脏支持的潜在策略。本研究旨在评估人成体肝干细胞在旋转式 BAL 中的分化情况。将肝干细胞以 3×10(8)个细胞/平方厘米的密度接种到聚砜膜过滤器上，并将过滤器连接到旋转生物反应器灌注系统（37°C，50 mL/min，48 h）。在 24 和 48 h 时评估细胞活力、细胞分化和代谢性能。比较人成体肝干细胞、成熟肝细胞和间充质干细胞在贴壁和旋转式 BAL 条件下产生的肝细胞生长因子的量。与贴壁培养的肝干细胞相比，在旋转式 BAL 中培养的肝干细胞产生的白蛋白量最高（p = 0.002）和氨诱导的尿素（p = 0.0001），细胞色素 P450 表达增加。值得注意的是，与肝细胞和间充质干细胞相比，在旋转式 BAL 中的肝干细胞产生了非常高量的肝细胞生长因子（p = 0.005）。此外，细胞失去了其干细胞标志物，并获得了几个成熟肝细胞的标志物。总之，旋转式 BAL 有利于肝干细胞向成熟肝细胞样细胞分化。
