马萨诸塞州总医院(MGH)的研究人员最近找到一种成功地体外培养肝细胞的方法，培养的肝细胞具有药物毒性筛选功能。
该研究发表在即将出版的PNAS杂志上。研究报告详细介绍了肝细胞如何在高氧条件和无动物血清的条件下生长，并如何快速发挥正常肝脏所具有的功能。
快速有效的筛选出具有毒副作用的药物能显著降低新药问世的成本。因为肝脏对代谢过程和体内药物清除具有重要作用，因此，筛选出肝脏毒性反应的药物是确保用药安全的关键。但动物研究并不能完全预测肝脏毒性反应，而在培养条件下的肝细胞又很快会失去代谢能力。
之前有研究表明，细胞培养中常用的动物血清对培养的肝细胞具有干扰作用，而且体外培养的肝细胞所处的氧气环境降低了10倍。因此，研究人员认为高氧、无血清环境是确保培养肝细胞的关键。
研究人员利用小鼠和人类的肝脏细胞进行研究，发现在无血清和含95%氧气的条件下，肝细胞很快能恢复正常代谢能力。这些培养的肝细胞还能或快或慢的进行药物清除，并且连续几周维持高水平的代谢能力。(生物谷Bioon.com)
生物谷推荐原始出处：
PNAS August 31, 2009, doi: 10.1073/pnas.0906820106
Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance
Srivatsan Kidambia, Rubin S. Yarmusha, Eric Novikb, Piyun Chaob, Martin L. Yarmusha and Yaakov Nahmiasa,c,1
aCenter for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02111;
bHμREL Corporation, Beverly Hills, CA 90211; and
cThe Selim and Rachel Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
The liver is a major site for the metabolism of xenobiotic compounds due to its abundant level of phase I/II metabolic enzymes. With the cost of drug development escalating to over $400 million/drug there is an urgent need for the development of rigorous models of hepatic metabolism for preclinical screening of drug clearance and hepatotoxicity. Here, we present a microenvironment in which primary human and rat hepatocytes maintain a high level of metabolic competence without a long adaptation period. We demonstrate that co-cultures of hepatocytes and endothelial cells in serum-free media seeded under 95% oxygen maintain functional apical and basal polarity, high levels of cytochrome P450 activity, and gene expression profiles on par with freshly isolated hepatocytes. These oxygenated co-cultures demonstrate a remarkable ability to predict in vivo drug clearance rates of both rapid and slow clearing drugs with an R2 of 0.92. Moreover, as the metabolic function of oxygenated co-cultures stabilizes overnight, preclinical testing can be carried out days or even weeks before other culture methods, significantly reducing associated labor and cost. These results are readily extendable to other culture configurations including three-dimensional culture, bioreactor studies, as well as microfabricated co-cultures.
