title: Cell therapy to remove excess copper in Wilson's disease.
abstract: To achieve permanent correction of Wilson's disease by a cell therapy approach, replacement of diseased hepatocytes with healthy hepatocytes is desirable. There is a physiological requirement for hepatic ATP7B-dependent copper (Cu) transport in bile, which is deficient in Wilson's disease, producing progressive Cu accumulation in the liver or brain with organ damage. The ability to repopulate the liver with healthy hepatocytes raises the possibility of cell therapy in Wilson's disease. Therapeutic principles included reconstitution of bile canalicular network as well as proliferation in transplanted hepatocytes, despite toxic amounts of Cu in the liver. Nonetheless, cell therapy studies in animal models elicited major differences in the mechanisms driving liver repopulation with transplanted hepatocytes in Wilson's disease versus nondiseased settings. Recently, noninvasive imaging was developed to demonstrate Cu removal from the liver, including after cell therapy in Wilson's disease. Such developments will help advance cell/gene therapy approaches, particularly by offering roadmaps for clinical trials in people with Wilson's disease.
authors.affiliation: Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Center, Departments of Medicine and Pathology, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, and Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics; D049109:Cell Proliferation; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006085:Graft Survival; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D006527:Hepatolenticular Degeneration / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D033581:Stem Cell Transplantation; D057170:Translational Research, Biomedical
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: bile; copper; excretion; liver; stem cell; transplantation