Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
Cell Transplant. 2013;22(2):231-42. doi: 10.3727/096368912X654939. Epub 2012 Aug 27.
At this time, the only definitive treatment of hepatic failure is liver transplantation. However, transplantation has been limited by the severely limited supply of human donor livers. Alternatively, a regenerative medicine approach has been recently proposed in rodents that describe the production of three-dimensional whole-organ scaffolds for assembly of engineered complete organs. In the present study, we describe the decellularization of porcine livers to generate liver constructs at a scale that can be clinically relevant. Adult ischemic porcine livers were successfully decellularized using a customized perfusion protocol, the decellularization process preserved the ultrastructural extracellular matrix components, functional characteristics of the native microvascular and the bile drainage network of the liver, and growth factors necessary for angiogenesis and liver regeneration. Furthermore, isolated hepatocytes engrafted and reorganized in the porcine decellularized livers using a human-sized organ culture system. These results provide proof-of-principle for the generation of a human-sized, three-dimensional organ scaffold as a potential structure for human liver grafts reconstruction for transplantation to treat liver disease.
此时，肝衰竭唯一确切的治疗方法是肝移植。然而，由于人类供体肝脏的严重短缺，移植受到了限制。最近，在啮齿动物中提出了一种再生医学方法，描述了三维全器官支架的生产，用于组装工程化完整器官。在本研究中，我们描述了猪肝脏的脱细胞化，以产生可在临床上相关的规模的肝构建体。使用定制的灌注方案成功地对缺血性成年猪肝脏进行了脱细胞化，脱细胞化过程保留了超微结构细胞外基质成分、天然微血管和肝脏胆汁引流网络的功能特性，以及血管生成和肝再生所需的生长因子。此外，使用人体大小的器官培养系统，在猪脱细胞化肝脏中植入并重新组织分离的肝细胞。这些结果为生成一个可用于人体肝脏移植重建的三维器官支架提供了原理证明，作为治疗肝脏疾病的人类肝脏移植物的潜在结构。
