title: Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice.
abstract: OBJECTIVE
  Transplantation of isolated hepatocytes holds great promise as an alternative to whole organ liver transplantation. For treatment of liver failure, access to the portal circulation has significant risks and intrahepatic hepatocyte engraftment is poor. In advanced cirrhosis, transplantation into an extrahepatic site is necessary and intrasplenic engraftment is short-lived. Strategies that allow repeated extrahepatic infusion of hepatocytes could improve the efficacy and safety of hepatocyte transplantation for the treatment of liver failure.
  
  
  METHODS
  A non-immunogenic self-assembling peptide nanofiber (SAPNF) was developed as a three-dimensional scaffold and combined with growth factors derived from a conditionally immortalized human hepatocyte cell line to engineer a hepatic tissue graft that would allow hepatocyte engraftment outside the liver.
  
  
  RESULTS
  The hepatic tissue constructs maintained hepatocyte-specific gene expression and functionality in vitro. When transplanted into skeletal muscle as an extrahepatic site for engraftment, the engineered hepatic grafts provided life-saving support in models of acute, fulminant, and chronic liver failure that recapitulates these clinical diseases.
  
  
  CONCLUSIONS
  SAPNF-engineered hepatic constructs engrafted and functioned as hepatic tissues within the muscle to provide life-sustaining liver support. These engineered tissue constructs contained no animal products that would limit their development as a therapeutic approach.
authors.affiliation: Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho, Okayama, Japan.
authors.forename: Nalu
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutierrez
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jose
authors.initials: J
authors.lastname: Caballero-Corbalan
authors.forename: Wael
authors.initials: W
authors.lastname: Hassan
authors.forename: Satoru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Masaya
authors.initials: M
authors.lastname: Iwamuro
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Fox
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002460:Cell Line; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D006801:Humans; D007273:Injections, Intramuscular; D017093:Liver Failure / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016031:Liver Transplantation; D051379:Mice; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal; D057139:Nanofibers; D036103:Nanotechnology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016042:Transplantation, Heterotopic