title: StrataGraft skin substitute is well-tolerated and is not acutely immunogenic in patients with traumatic wounds: results from a prospective, randomized, controlled dose escalation trial.
abstract: OBJECTIVE
  The goal of this study was to assess the immunogenicity and antigenicity of StrataGraft skin tissue in a randomized phase I/II clinical trial for the temporary management of full-thickness skin loss.
  
  
  BACKGROUND
  StrataGraft skin tissue consists of a dermal equivalent containing human dermal fibroblasts and a fully stratified, biologically active epidermis derived from Near-diploid Immortalized Keratinocyte S (NIKS) cells, a pathogen-free, long-lived, consistent, human keratinocyte progenitor.
  
  
  METHODS
  Traumatic skin wounds often require temporary allograft coverage to stabilize the wound bed until autografting is possible. StrataGraft and cadaveric allograft were placed side by side on 15 patients with full-thickness skin defects for 1 week before autografting. Allografts were removed from the wound bed and examined for allogeneic immune responses. Immunohistochemistry and indirect immunofluorescence were used to assess tissue structure and cellular composition of allografts. In vitro lymphocyte proliferation assays, chromium-release assays, and development of antibodies were used to examine allogeneic responses.
  
  
  RESULTS
  One week after patient exposure to allografts, there were no differences in the numbers of T or B lymphocytes or Langerhans cells present in StrataGraft skin substitute compared to cadaver allograft, the standard of care. Importantly, exposure to StrataGraft skin substitute did not induce the proliferation of patient peripheral blood mononuclear cells to NIKS keratinocytes or enhance cell-mediated lysis of NIKS keratinocytes in vitro. Similarly, no evidence of antibody generation targeted to the NIKS keratinocytes was seen.
  
  
  CONCLUSIONS
  These findings indicate that StrataGraft tissue is well-tolerated and not acutely immunogenic in patients with traumatic skin wounds. Notably, exposure to StrataGraft did not increase patient sensitivity toward or elicit immune responses against the NIKS keratinocytes. We envision that this novel skin tissue technology will be widely used to facilitate the healing of traumatic cutaneous wounds.This study was registered at www.clinicaltrials.gov (NCT00618839).
authors.affiliation: Stratatech Corporation, Madison, WI, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Centanni
authors.forename: Joely A
authors.initials: JA
authors.lastname: Straseski
authors.forename: April
authors.initials: A
authors.lastname: Wicks
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Hank
authors.forename: Cathy A
authors.initials: CA
authors.lastname: Rasmussen
authors.forename: Mary A
authors.initials: MA
authors.lastname: Lokuta
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schurr
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Foster
authors.forename: Lee D
authors.initials: LD
authors.lastname: Faucher
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Caruso
authors.forename: Allen R
authors.initials: AR
authors.lastname: Comer
authors.forename: B Lynn
authors.initials: BL
authors.lastname: Allen-Hoffmann
mesh_terms: D000328:Adult; D000368:Aged; D002102:Cadaver; D062109:Dermatologic Surgical Procedures; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D015601:Injury Severity Score; D015603:Keratinocytes / Q000637:transplantation; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011446:Prospective Studies; D012867:Skin / Q000293:injuries*; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods*; D017768:Skin, Artificial; D017695:Soft Tissue Injuries / Q000276:immunology / Q000601:surgery*; D014181:Transplantation Immunology / Q000502:physiology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014945:Wound Healing / Q000502:physiology*