Tanaka Kimiaki, Soto-Gutierrez Alejandro, Navarro-Alvarez Nalu, Rivas-Carrillo Jorge David, Jun Hee-Sook, Kobayashi Naoya
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Cell Transplant. 2006;15(10):855-64. doi: 10.3727/000000006783981332.
Since Berry and Friend developed methods to isolate hepatocytes from the liver by a collagenase digestion technique in 1969, studies in laboratory animals have demonstrated that hepatocyte transplantation could potentially be used for the treatment of liver failure and inborn errors of liver-based metabolism. Healthy human hepatocytes are an ideal source for hepatocyte transplantation; however, their relative scarcity is one of the major drawbacks, further compounded by the competing demands of liver transplantation. Notably, most of the hepatocytes are isolated from discarded livers that are not suitable for organ transplantation for a variety of reasons, including excessive fat content. Importantly, the hepatocyte isolation procedure itself exerts major stress on hepatocytes by the disruption of cell-to-cell and cell-to-matrix contacts, resulting in hepatocytic apoptosis. Prevention of apoptosis would maximize yield of healthy cells and maintain hepatocyte differentiated function in culture. In this review, we describe methods to prevent apoptosis by utilizing both antiapoptotic molecules and matrices. We also introduce a new type of liver tissue engineering, hepatocyte sheet transplantation, which utilizes unwoven cloth having a cellular adhesive property.
自1969年贝里和弗里德开发出通过胶原酶消化技术从肝脏中分离肝细胞的方法以来，对实验动物的研究表明，肝细胞移植有可能用于治疗肝衰竭和基于肝脏代谢的先天性疾病。健康的人肝细胞是肝细胞移植的理想来源；然而，它们相对稀缺是主要缺点之一，肝脏移植的竞争需求进一步加剧了这一问题。值得注意的是，大多数肝细胞是从因各种原因（包括脂肪含量过高）而不适用于器官移植的废弃肝脏中分离出来的。重要的是，肝细胞分离过程本身会通过破坏细胞间和细胞与基质的接触对肝细胞施加重大压力，导致肝细胞凋亡。预防凋亡将最大限度地提高健康细胞的产量，并在培养中维持肝细胞的分化功能。在这篇综述中，我们描述了利用抗凋亡分子和基质来预防凋亡的方法。我们还介绍了一种新型的肝脏组织工程——肝细胞片移植，它利用具有细胞粘附特性的无纺布。
