Soto-Gutierrez Alejandro, Navarro-Alvarez Nalu, Rivas-Carrillo Jorge D, Tanaka Kimiaki, Chen Yong, Misawa Haruo, Okitsu Teru, Noguchi Hirofumi, Tanaka Noriaki, Kobayashi Naoya
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Transplantation. 2007 Jan 27;83(2):129-37. doi: 10.1097/01.tp.0000250561.14108.03.
Acute liver failure (ALF) is a serious condition that has a high mortality rate. Construction of an efficient culture and transplantation engineering system of hepatic tissue is an important approach to treat patients suffering from ALF to provide short-term hepatic support until the damaged liver spontaneously recovers or a donor liver becomes available for transplantation. Here, we evaluate the construction and transplantation of an engineered hepatic tissue (EHT) using primary isolated hepatocytes cultured onto polyaminourethane (PAU)-coated, nonwoven polytetrafluoroethylene (PTFE) fabric.
The isolated hepatocytes cultured onto PAU-coated PTFE fabric were able to adhere and spread over the individual fibers of the net and formed hepatic clusters after 3 days, such clusters revealed Gap junctions and well-developed bile canaliculi.
When PAU-coated PTFE was utilized, ammonia-, and diazepam- metabolizing capacities and albumin production ability were significantly increased compared with collagen control. To test the function of this hepatic tissue in vivo, we transplanted a nonwoven PAU-coated PTFE fabric inoculated with one million hepatocytes on the surface of the spleen of Balb/c mice suffering from ALF induced by 90% hepatectomy, and found that this EHT prolonged the survival of liver failure-induced mice without adverse effects. Ultrastructure analyses showed good attachment of the cells on the surface of PTFE fabric and strong albumin expression seven days after the newly formed hepatic tissue was transplanted.
We have here demonstrated the efficient construction and transplantation of hepatic tissue using primary hepatocytes and PAU-coated PTFE fabric.
急性肝衰竭（ALF）是一种严重疾病，死亡率很高。构建高效的肝组织培养和移植工程系统是治疗ALF患者的重要方法，可为患者提供短期肝支持，直至受损肝脏自发恢复或有供体肝脏可用于移植。在此，我们评估了使用原代分离肝细胞在聚氨基聚氨酯（PAU）涂层的非织造聚四氟乙烯（PTFE）织物上培养构建并移植工程化肝组织（EHT）的情况。
培养在PAU涂层PTFE织物上的分离肝细胞能够附着并铺展在网的单根纤维上，3天后形成肝簇，这些肝簇显示有缝隙连接和发育良好的胆小管。
与胶原蛋白对照组相比，使用PAU涂层PTFE时，氨和地西泮的代谢能力以及白蛋白产生能力显著提高。为了在体内测试这种肝组织的功能，我们将接种了100万个肝细胞的PAU涂层非织造PTFE织物移植到90%肝切除诱导的ALF的Balb/c小鼠脾脏表面，发现这种EHT延长了肝衰竭诱导小鼠的存活时间且无不良影响。超微结构分析显示，新形成的肝组织移植7天后，细胞在PTFE织物表面附着良好且白蛋白表达强烈。
我们在此证明了使用原代肝细胞和PAU涂层PTFE织物可高效构建并移植肝组织。
