Tolboom Herman, Pouw Roos, Uygun Korkut, Tanimura Yoko, Izamis Maria-Louisa, Berthiaume François, Yarmush Martin L
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tissue Eng. 2007 Aug;13(8):2143-51. doi: 10.1089/ten.2007.0101.
Current techniques for the preservation of donor livers typically rely on cold temperatures (approximately 0-4 degrees C) to slow down metabolic processes. Recently, normothermic extracorporeal liver perfusion (NELP) has regained interest as a potentially promising approach for long-term liver preservation. Unlike cold-storage techniques, NELP attempts to maintain the liver in a near physiological environment, thus enabling normal metabolic and tissue repair processes to take place, which may help in the recovery of ischemically damaged and fatty donor livers, both of which represent significant untapped sources of donor livers. However, NELP is technically more complex than cold-storage techniques, and the lack of standardized small animal models limits its development. Here we describe a rat NELP system that is simple and cost-effective to run. We show that rat livers that underwent NELP for 6 h could be routinely transplanted into syngeneic recipient rats with excellent 1-month survival. During perfusion, the release of cytosolic enzymes, bile and urea production, and oxygen uptake rate could be readily monitored, thus providing a comprehensive picture of hepatic function before transplantation. This system will help in the optimization of NELP in several ways, such as for the improvement of perfusion conditions and the development of quantitative metabolic criteria for hepatic viability.
目前用于保存供体肝脏的技术通常依靠低温(约0-4摄氏度)来减缓代谢过程。最近,常温体外肝脏灌注(NELP)作为一种潜在的长期肝脏保存方法重新引起了人们的关注。与冷藏技术不同,NELP试图将肝脏维持在接近生理的环境中,从而使正常的代谢和组织修复过程得以进行,这可能有助于缺血损伤和脂肪肝供体肝脏的恢复,这两种肝脏都是尚未充分利用的重要供体肝脏来源。然而,NELP在技术上比冷藏技术更复杂,并且缺乏标准化的小动物模型限制了其发展。在此,我们描述了一种运行简单且成本效益高的大鼠NELP系统。我们表明,经过6小时NELP处理的大鼠肝脏可以常规移植到同基因受体大鼠体内,1个月存活率良好。在灌注过程中,可以很容易地监测胞质酶的释放、胆汁和尿素的产生以及氧摄取率,从而在移植前全面了解肝功能。该系统将在多个方面有助于优化NELP,例如改善灌注条件以及制定肝脏活力的定量代谢标准。