A study of hepatic support unit using implantable porous hydoroxyapatite ceramics combined with isolated hepatocytes or fetal liver fragments.

本研究计划利用可植入的多孔羟基磷灰石陶瓷(HXA)与分离的肝细胞相结合，研制一种新型的肝支持装置。取成年Wistar大鼠肝细胞或18~19孕鼠胎肝细胞作为供体。将这些肝细胞或胎肝碎片植入HXA，并将几个HXA移植到同基因大鼠的大网膜。HXA有许多细长的毛孔，因此有望为肝细胞的长期存活和增殖提供良好的环境。本研究通过组织化学和超微结构观察，评价了肝细胞移植入HXA后在HXA内的存活情况。移植后24小时可检测到多个存活的成体肝细胞，但大部分在移植后48小时内消失。另一方面，移植后1个月，HXA腔内仍可见存活肝细胞形成胰岛。此外，这些肝细胞的某些功能表现为PAS阳性的肝细胞和BRDU和增殖细胞核抗原免疫化学反应阳性的增殖性肝细胞。然而，我们也观察到胆管细胞的快速增殖。基于这些发现，我们证实了利用可植入的多孔HXA结合分离的肝细胞或胎肝片段来创造新的肝支持单元的小型装置。

The research project was planed to develop a new device of hepatic support unit using implantable porous hydoroxyapatite ceramics(HXA) combined with isolated hepatocytes. Hepatocytes isolated from adult wistarrat or fetal liver prepared from 18-19 gestation rat were used as donor. These hepatocytes or fetal liver fragments were implanted into HXA, and several HXAS were transplanted into omentum of syngeneic rat. HXA possesses many long and narrow pores, therefore favorable environment for the long surval of hepatocytes with proliferation would be expected. In this study, we assessed the survival of hepatocyte in HXA after transplanted into the abdominal cavity by histological approach using hisotchemical and fine structural examinations.At 24hours after transplantation (TX), several viable adult hepatocytes were detected, but most of them disappeared within 48 hours after TX.On the other hand, viable hepatocytes forming islets in the cavity of HXA even one month after TX into omentum. Moreover, these hepatocytes revealed some functional aspects showing pas positive hepatocytes and proliferating hepatocytes which were positive for BRDU and PCNA immunochemical reactions. However, rapid proliferation of bile ductal cells were also observed.Based on these finding, we confirmed that it enable for us to create new small devices for hepatic support unit using implantable porous HXA combined with isolated hepatocytes or fetal liver fragments.