title: Liver-Regenerative Transplantation: Regrow and Reset.
abstract: Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)-derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: A
authors.initials: A
authors.lastname: Collin de l'Hortet
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: K
authors.initials: K
authors.lastname: Takeishi
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: J
authors.initials: J
authors.lastname: Guzman-Lepe
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Handa
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukumitsu
authors.affiliation: Organovo Holdings Inc., San Diego, CA.
authors.forename: K
authors.initials: K
authors.lastname: Dorko
authors.affiliation: Organovo Holdings Inc., San Diego, CA.
authors.forename: S C
authors.initials: SC
authors.lastname: Presnell
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.|Thomas E. Starzl Transplantation Institute and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: A
authors.initials: A
authors.lastname: Soto-Gutierrez
mesh_terms: D000818:Animals; D006801:Humans; D008107:Liver Diseases / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D016031:Liver Transplantation; D023822:Tissue Engineering / Q000379:methods*