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

本研究拟利用植入式多孔羟基磷灰石陶瓷（HXA）与离体肝细胞复合，研制一种新型的肝支持装置。从成年Wistar大鼠或从18-19胎龄大鼠制备的胎肝中分离的肝细胞用作供体。将这些肝细胞或胎肝碎片植入HXA中，并将几个HXAS移植到同系大鼠网膜中。HXA具有许多狭长的孔，因此，预期HXA具有有利于肝细胞长期存活和增殖的环境。本研究采用组织化学和精细结构观察方法，对HXA腹腔内移植后肝细胞的存活情况进行了观察，发现移植后24小时（TX）仍有存活的肝细胞，但大多数肝细胞在TX后48小时内消失，另一方面，即使在TX进入网膜后1个月，仍有存活的肝细胞在HXA腔内形成胰岛。此外，这些肝细胞揭示了一些功能方面，显示pas阳性肝细胞和增殖肝细胞，其对BRDU和PCNA免疫化学反应呈阳性。基于这些发现，我们证实，它使我们能够创建新的小型装置的肝支持单元使用植入式多孔HXA结合分离的肝细胞或胎肝碎片。

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.