Demonstrating Potential of Cell Therapy for Wilson's Disease with the Long-Evans Cinnamon Rat Model.
Wilson's disease (WD) is characterized by the inability to excrete copper (Cu) from the body with progressive tissue injury, especially in liver and brain. The molecular defect in WD concerns mutations in ATP7B gene leading to loss of Cu transport from the hepatocyte to the bile canaliculus. While drugs, e.g., Cu chelators, have been available for several decades, these must be taken lifelong, which can be difficult due to issues of compliance or side effects. Many individuals may require liver transplantation, which can also be difficult due to donor organ shortages. Therefore, achieving permanent cures via cell or gene therapy are of great interest for WD. Cell therapy is feasible because transplanted hepatocytes can integrate in liver parenchyma and restore deficient functions, including transport of Cu into bile. The availability of authentic animal models that recapitulate hepatic WD, especially the Long-Evans Cinnamon (LEC) rat, has advanced cell transplantation research in WD. We describe requirements for cell therapy in animal models with several standardized methods for studies to test or refine cell therapy strategies in WD.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Fadi Luc
FL
Jaber
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Yogeshwar
Y
Sharma
Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Ullmann Building, Room 625, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. sanjeev.gupta@einstein.yu.edu.
Sanjeev
S
Gupta
D000818:Animals; D017690:Cell Transplantation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D065669:Hepatobiliary Elimination; D022781:Hepatocytes / Q000637:transplantation*; D006527:Hepatolenticular Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects; D009154:Mutation; D051381:Rats; D020332:Rats, Inbred LEC / Q000502:physiology* / Q000601:surgery
D003300:Copper; C550619:Atp7b protein, rat; D000073840:Copper-Transporting ATPases
Biliary transport; Cell transplantation; Copper; Liver injury; Regeneration; Wilson’s disease