Transplantation of a fetal liver cell-loaded hyaluronic acid sponge onto the mesentery recovers a Wilson's disease model rat.
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.
Katsuda
Takeshi
T
Institute of Industrial Science (IIS), The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan. katsuda@iis.u-tokyo.ac.jp
Teratani
Takumi
T
Ochiya
Takahiro
T
Sakai
Yasuyuki
Y
D000818:Animals; D003300:Copper / Q000378:metabolism; D004195:Disease Models, Animal; D006085:Graft Survival; D022781:Hepatocytes / Q000637:transplantation*; D006527:Hepatolenticular Degeneration / Q000628:therapy*; D006820:Hyaluronic Acid; D007565:Jaundice / Q000517:prevention & control; D016031:Liver Transplantation / Q000379:methods*; D019164:Liver, Artificial; D011161:Porifera; D051381:Rats; D020318:Rats, Long-Evans; D013152:Splanchnic Circulation; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome
D003300:Copper; D006820:Hyaluronic Acid