Allogeneic versus Xenogeneic Immune Reaction to Bioengineered Skin Grafts

Abstract

There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a hyperproliferative epidermis. CSS (control and KGF modified) and neonatal human foreskins were evaluated by immunohistochemistry for the expression of MHC class I and II. To study allograft rejection, grafts were transplanted to human peripheral blood mononuclear cell (huPBMC)-reconstituted SCID mice. To study xenograft rejection, grafts were transplanted to immunocompetent mice. Graft survival and immune reaction were assessed visually and microscopically. After transplantation, control CSS formed a normal differentiated epidermis, whereas KGF CSS formed a hyperproliferative epidermis. Control and KGF CSS expressed class I similar to neonatal foreskin, but did not express class II. In the allograft model, rejection of neonatal foreskins was between 5 and 9 days. In contrast, neither control nor KGF CSS was rejected by huPBMC-SCID mice. Histology showed dense mononuclear cell infiltration in human foreskins, with few, if any, mononuclear cells in control or KGF CSS. In contrast to the allogeneic reaction, CSS (control and KGF) were rejected in the xenograft model, but rejection was delayed (9-21 days) compared with neonatal skin (5-8 days). Humanized SCID mice rejected allografts of human neonatal foreskins, but did not reject control CSS or KGF CSS, even though the KGF CSS formed a hyperproliferative epidermis. Rejection of control and KGF CSS by immunocompetent mice in a xenograft model was comparable and their survival was significantly prolonged compared with neonatal skin. These results demonstrate that control CSS and hyperproliferative KGF CSS are less immunogenic than normal human skin and that sustained hyperproliferation of the epidermis does not accelerate rejection.

A multi-step method for preparation of porcine small intestinal submucosa (SIS)

“…Indeed, the histological observation, qPCR analysis of porcine DAP12 gene, and SIS transplantation into rats all demonstrated the usefulness of this current method for preparation of SIS for clinical use. If the product contains porcine cell debris, xenogeneic and allogeneic cellular antigens could induce an adverse inflammatory response by the host [36,37]. Our method has effectively removed cells and cell debris from the small intestinal submucosa, which is necessary to minimize or avoid an adverse immunologic response by xenogenic recipients of the SIS material.…”

Local expression of indoleamine 2,3-dioxygenase suppresses T-cell-mediated rejection of an engineered bilayer skin substitute

“…Although many of these products provide adequate wound coverage and an environment in which cells may grow, none comprise both dermal and epidermal components 5 . More importantly, there remains a need for an for an allogeneic, patient‐ready skin substitute comprising both epidermal and dermal components that will withstand antigen‐specific rejection in the absence of an immunosuppression regime 35,36 . Therefore, the primary goal of this study was to develop and evaluate the functionality of an engineered skin substitute containing a stratified epidermal layer of primary keratinocytes and a dermal matrix containing IDO expressing fibroblasts in both in vitro and in vivo models.…”

Histologic examination of decellularized porcine intestinal submucosa extracellular matrix (CorMatrix) in pediatric congenital heart surgery

“…Although the current materials have greatly improved long-term outcomes in cardiac surgical candidates, patients continue to face adverse outcomes secondary to graft degeneration, calcification, stenosis, and lack of growth, with inflammatory response, cicatrization, and aneurysm formation [1][2][3]. Cardiovascular Pathology xxx (2015) xxx-xxx CorMatrix as well as other decellularized biologic scaffolds appear advantageous in cardiac repair as they avoid sensitization associated with homograft materials as xenogeneic and allogeneic cellular antigens are recognized as foreign by the host [4][5][6]. Decellularized biologic scaffolds also possess the theoretical potential for growth by providing a scaffold for host cells to reconstruct related tissues.…”