title: Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.
abstract: Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.
authors.affiliation: Department of Cell Biology and PhysiologyUniversity of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Turner
authors.forename: Eliane
authors.initials: E
authors.lastname: Wauthier
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lozoya
authors.forename: Randall
authors.initials: R
authors.lastname: McClelland
authors.forename: James E
authors.initials: JE
authors.lastname: Bowsher
authors.forename: Claire
authors.initials: C
authors.lastname: Barbier
authors.forename: Glenn
authors.initials: G
authors.lastname: Prestwich
authors.forename: Edward
authors.initials: E
authors.lastname: Hsu
authors.forename: David A
authors.initials: DA
authors.lastname: Gerber
authors.forename: Lola M
authors.initials: LM
authors.lastname: Reid
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000601:surgery; D002478:Cells, Cultured; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000627:therapeutic use; D008099:Liver / Q000166:cytology / Q000601:surgery*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D006820:Hyaluronic Acid