title: Survival of Allogeneic Self-Assembled Cultured Skin.
abstract: Deficiency of autologous skin for reconstruction of severe wounds is a major problem in plastic surgery. Autologous substitutes can provide additional coverage, but due to the duration of production, treatment is significantly delayed. The allogeneic approach offers a potential of having an off-the-shelf solution for the immediate application.
  
  
  
  In this study, we assess the engraftment and immunogenicity of allogeneic bilayered bioengineered skin prepared by a self-assembly method. Bioengineered skin has the potential immunological advantage of lacking passenger leukocytes including antigen-presenting cells. The skin constructs were transplanted across major histocompatibility complex (MHC) barriers in a porcine animal model. Animals received a second grafting of the same skin construct 7 weeks after the first set of grafts together with MHC-matched constructs to assess for clinical sensitization.
  
  
  
  All alloconstructs successfully engrafted with histologic evidence of neovascularization by day 4. Complete cellular rejection and tissue loss occurred by day 8 for most grafts. After the second application, accelerated rejection (<4 days) took place with the development of swine MHC-specific cytotoxic alloantibody.
  
  
  
  These data demonstrate preclinically that self-assembled allogeneic constructs engraft and reject similar to allogeneic skin despite the absence of professional donor antigen-presenting cells.
authors.affiliation: 1 Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 2 Department of Pathology, Massachusetts General Hospital, Boston, MA. 3 Preclinical Research and Development Laboratory, Organogenesis Inc. Canton, MA. 4 Plastic Surgery Research Laboratory, Massachusetts General Hospital, Boston, MA.
authors.forename: Mihail
authors.initials: M
authors.lastname: Climov
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Matar
authors.forename: Evan A
authors.initials: EA
authors.lastname: Farkash
authors.forename: Erika
authors.initials: E
authors.lastname: Medeiros
authors.forename: Jizeng
authors.initials: J
authors.lastname: Qiao
authors.forename: Edward
authors.initials: E
authors.lastname: Harrington
authors.forename: Ashley
authors.initials: A
authors.lastname: Gusha
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Musa
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Mark
authors.initials: M
authors.lastname: Randolph
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Bollenbach
authors.forename: Christene A
authors.initials: CA
authors.lastname: Huang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D006084:Graft Rejection; D007518:Isoantibodies / Q000096:biosynthesis; D012867:Skin; D016038:Skin Transplantation / Q000009:adverse effects; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering; D014184:Transplantation, Homologous
chemical_list: D007518:Isoantibodies