Local expression of indoleamine 2,3-dioxygenase suppresses T-cell-mediated rejection of an engineered bilayer skin substitute.
Engineered skin substitutes (ESSs) comprising both keratinocytes and fibroblasts can afford many advantages over the use of autologous keratinocyte grafts for the treatment of full-thickness and partial-thickness burns. In this study, we investigated the efficacy of a novel ESS containing both genetically altered fibroblasts that express the immunosuppressive factor indoleamine 2,3-dioxygenase (IDO) and primary keratinocytes from a nonautologous source to confer immune protection of xenogeneic cells cultured in a bilayer ESS. The results show that engraftment of IDO expressing skin substitutes on the back of rats significantly improves healing progression over 7 days compared with both nontreated and non-IDO-expressing skin substitutes (p<0.001). Immuno-staining of CD3 and CD31 suggests that IDO-expressing skin substitutes significantly suppress T cell infiltration (p<0.001) and improve neovascularization by four-fold (12.6±1.2 vs. 3.0±1.0 vessel-like structure/high power field), respectively. In conclusion, we found that IDO expression can improve the efficacy of nonautologous ESS for the purpose of wound healing by mitigating T-cell infiltration as well as promoting vascularization of the graft.
Burn and Wound Healing Research Laboratory, Department of Surgery, Immunity and Infection Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Farshad
F
Forouzandeh
Reza B
RB
Jalili
Ryan V
RV
Hartwell
Sarah E
SE
Allan
Steven
S
Boyce
Dorothy
D
Supp
Aziz
A
Ghahary
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D005822:Genetic Vectors; D006084:Graft Rejection / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism* / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D017768:Skin, Artificial; D013601:T-Lymphocytes / Q000378:metabolism*; D023822:Tissue Engineering; D014162:Transfection; D014945:Wound Healing
D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase