title: Lack of cross-sensitization between α-1,3-galactosyltransferase knockout porcine and allogeneic skin grafts permits serial grafting.
abstract: BACKGROUND
  The current standard of care for burns requiring operative treatment consists of early burn excision and autologous split-thickness skin grafting. However, in large burns, sufficient donor sites may not be available to achieve total coverage, necessitating temporary coverage with allogeneic human cadaver skin grafts or synthetic skin substitutes. A previous study from this laboratory demonstrated that skin grafts from alpha-1,3 galactosyltransferase knockout (GalT-KO) miniature swine enjoyed survival comparable to that of allogeneic skin grafts in baboons.
  
  
  METHODS
  In the present study, we have evaluated the immune response against sequential GalT-KO and allogeneic skin grafts to determine whether such serial grafts could extend the period of temporary wound coverage before definitive grafting with autologous skin.
  
  
  RESULTS
  We report that rejection of primary GalT-KO skin grafts led to an anti-xenogeneic humoral response with no evidence for sensitization to alloantigens nor acceleration of rejection of allogeneic skin grafts. Similarly, presensitization with allogeneic skin did not lead to accelerated rejection of xenogeneic skin.
  
  
  CONCLUSIONS
  These data suggest that GalT-KO skin grafts could provide an early first-line treatment in the management of severe burns that would not preclude subsequent use of allografts, and that serial grafting of GalT-KO skin and allogeneic skin could potentially be used to provide an extended period of temporary burn wound coverage.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA. 2 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 3 Department of Biology, Emmanuel College, Boston, MA. 4 Address correspondence to Curtis L. Cetrulo, Jr, M.D., F.A.C.S., Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East Building, 149-9019, 13th Street, Boston, MA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Albritton
authors.forename: David A
authors.initials: DA
authors.lastname: Leonard
authors.forename: Angelo
authors.initials: A
authors.lastname: Leto Barone
authors.forename: Josh
authors.initials: J
authors.lastname: Keegan
authors.forename: Christopher
authors.initials: C
authors.lastname: Mallard
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Josef M
authors.initials: JM
authors.lastname: Kurtz
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Cetrulo
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003429:Cross Reactions; D004195:Disease Models, Animal; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D056724:Immunity, Humoral; D010215:Papio; D012867:Skin / Q000276:immunology* / Q000293:injuries / Q000378:metabolism; D016038:Skin Transplantation / Q000009:adverse effects / Q000379:methods*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014945:Wound Healing
chemical_list: D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase