Transplantation of a fetal liver cell-loaded hyaluronic acid sponge onto the mesentery recovers a Wilson's disease model rat
Transplantation of a fetal liver cell-loaded hyaluronic acid sponge onto the mesentery recovers a Wilson's disease model rat
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DOI：
10.1093/jb/mvq063
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发表时间：
2010-09-01
影响因子：
2.7
通讯作者：
Sakai, Yasuyuki
中科院分区：
文献类型：
--
作者：
Katsuda, Takeshi;Teratani, Takumi;Sakai, Yasuyuki
辅助肝是肝移植的一种很有前途的选择。然而，大量成熟肝细胞的使用，尽管其功能高，但在临床环境中受到限制。在这里，我们提出了一种新型移植系统，通过将胎肝细胞（FLC）作为细胞来源、肠系膜作为移植部位和透明质酸（HA）海绵作为细胞支架，显着改善患病动物。我们将野生型Long Evans Agglomerate大鼠FLC嵌入HA海绵中移植到Long Evans Cinnamon（LEC）大鼠（Wilson病的动物模型）的肠系膜上。加载FLC的HA海绵成功移植，从而防止黄疸。因此，经处理的动物显示血铜浓度显著降低，从而导致血清总胆红素和直接胆红素显著降低，以及白蛋白产率显著增加。此外，宿主肝脏的苏木精和伊红染色表明，给药动物门静脉周围区域的纤维化程度减轻。总之，我们将负载FLC的HA海绵移植到肠系膜血管上，导致厚的、具有血管的肝样组织，并且肝组织工程因此对LEC大鼠的铜代谢缺陷表现出显著的治疗效果。
An auxiliary liver represents a promising alternative for liver transplantation. The use of a large amount of mature hepatocytes, however, despite their high function, is limited in a clinical setting. Here, we propose a novel transplantation system that dramatically improved a diseased animal by incorporating fetal liver cells (FLCs) as a cell source, the mesentery as a transplantation site and a hyaluronic acid (HA) sponge as a cell scaffold. We transplanted wild-type Long Evans Agouti rat FLCs embedded in HA sponges onto the mesentery of Long Evans Cinnamon (LEC) rats, an animal model for Wilson's disease. The FLC-loaded HA sponges successfully grafted and consequently prevented jaundice. Accordingly, the treated animals showed a significant reduction in blood copper concentration, which consequently led to significant decreases in serum total bilirubin and direct bilirubin, and to a significant increase in albumin productivity. Furthermore, haematoxylin and eosin staining of the host livers demonstrated that fibrosis at the periportal area was moderated in the treated animals. In conclusion, we transplanted FLC-loaded HA sponges onto the mesenteric blood vessels, leading to thick, liver-like tissue possessing blood vessels, and the liver tissue engineered thus exhibited a remarkable therapeutic effect on the copper metabolism deficiency of LEC rats.