Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nat Med. 2010 Jul;16(7):814-20. doi: 10.1038/nm.2170. Epub 2010 Jun 13.
Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.
原位肝移植是治疗严重肝功能衰竭的唯一方法,但目前受到供体器官短缺的限制。一个迄今为止限制组织工程肝移植物发展的技术挑战是氧气和营养物质的运输。在这里,我们展示了一种使用去细胞化肝基质生成可移植肝移植物的新方法。去细胞化过程保留了天然微血管网络的结构和功能特征,允许成年肝细胞有效地再细胞化肝基质,并随后进行体外培养的灌注。再细胞化的移植物支持肝特异性功能,包括白蛋白分泌、尿素合成和细胞色素 P450 表达,其水平与体外正常肝脏相当。再细胞化的肝移植物可以移植到大鼠体内,在最小的缺血损伤下支持肝细胞的存活和功能。这些结果为生成可移植肝移植物作为治疗肝病的潜在方法提供了原理证明。