Department of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Cell Transplant. 2010;19(6):799-806. doi: 10.3727/096368910X508915. Epub 2010 Jun 23.
Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell-cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival.
尽管肝移植已成为一种标准治疗方法，但肝脏疾病的死亡率仍然很高。目前，肝细胞移植已被提出作为另一种有前途的策略。一个限制是人类肝脏作为肝细胞来源的可用性。由于供应不受限制，使用猪肝细胞可能会解决这个问题。无论来源如何，一旦分离的肝细胞由于天然微环境的丧失而失去特定的功能。出于这个原因，我们测试了自组装肽纳米纤维（SAPNF）的能力，以提供临时的三维（3D）支持与细胞相互作用，从而控制它们在体内的功能。将分离的猪肝细胞嵌入 SAPNF 或胶原蛋白 I 中，并通过直接注射到 90%肝切除术后患有急性肝衰竭（ALF）的 SCID 小鼠的脾髓中来移植。与对照相比，SAPNF 猪肝细胞移植产生的植入物远优于使用胶原蛋白获得的植入物，并延长了 ALF 小鼠的存活时间。使用透射电子显微镜进行的超微结构评估表明细胞间广泛的通讯和维持肝细胞结构。移植的 SAPNF 肝细胞表现出更高的白蛋白和 PAS 表达，并且通过 TUNEL 染色评估的凋亡事件更少。在真正的 3D 网络中培养的肝细胞允许在体内维持分化功能，并且一旦在差异很大的物种之间移植，就可以在小鼠中纠正急性肝衰竭并延长其存活时间。
