StrataGraft Skin Substitute Is Well-tolerated and Is Not Acutely Immunogenic in Patients With Traumatic Wounds

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. Summary Background Data StrataGraft skin tissue consists of a dermal equivalent containing human dermal fibroblasts and a fully-stratified, biologically active epidermis derived from 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 one week prior to 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 this novel skin tissue technology will be widely used to facilitate the healing of traumatic cutaneous wounds.

Clinical Evaluation of NIKS-Based Bioengineered Skin Substitute Tissue in Complex Skin Defects: Phase I/IIa Clinical Trial Results

“…No acute inflammatory infiltrate was found in any of the allografted tissues. The data presented 9 show that after placement of NIKS-based BSS for 1 week in full-thickness wounds, normal tissue architecture was maintained with no substantial inflammatory infiltrate seen. These data are suggestive that this BSS did not induce an acute inflammatory response in patients with fullthickness skin loss and is in agreement with clinical experience with other allogeneic products as described above.…”

“…Results of this trial demonstrate that this BSS tissue, a biologically active, fully stratified, temporary wound covering generated using NIKS keratinocytes, was well tolerated and showed no evidence of safety concerns. 8,9 Expression of the host defense peptide, human beta defensin-3, is increased in NIKS-based BSS Due to the increasing importance of HDPs in combating infection and modulating host immune responses, prior to clinical evaluation the expression of human beta defensin-3 (HBD-3) was examined. Quantitative polymerase chain reaction analysis revealed an approximately 8-fold increase in HBD-3 in NIKS-based BSS when compared to skin tissue from either primary human epidermal keratinocytes or the parental keratinocytes from which NIKS arose.…”

“…1,7 A living, full-thickness, allogeneic, human skin substitute generated from NIKS cells (NIKS-based BSS) to provide immediate wound coverage and promote wound healing has been recently developed and is being clinically tested. 8,9 This review will focus on the first-in-humans study of this BSS. NIKS cells are a near-diploid neonatal human epidermal keratinocyte progenitor cell line that exhibit keratinocyte-specific growth and differentiation characteristics yet maintain an extended lifespan in vitro.…”

Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes

“…Allogeneic skin substitutes generated with NIKS keratinocytes have been evaluated in a Phase I/IIa clinical trial for the temporary management of traumatic skin wounds. 15,16 NIKS-based skin substitutes were found to be comparable to the standard of care of cadaver skin, were well tolerated, and did not elicit acute allogeneic immune responses to NIKS cells in treated patients. No therapy-related adverse events were observed.…”

A Bioengineered Human Skin Tissue for the Treatment of Infected Wounds

“…22,23 However, clinical findings with BSS therapies suggest that cultured skin tissue is unlikely to be acutely rejected in humans. [24][25][26][27][28] Skin substitutes are gradually replaced by the patient's skin with no excessive inflammation or other signs of acute rejection. [25][26][27][28] Finally, a limitation of all cell-based BSS therapies is the high cost of manufacturing.…”