Survival of Allogeneic Self-Assembled Cultured Skin. 2016

Mihail Climov, and Abraham J Matar, and Evan A Farkash, and Erika Medeiros, and Jizeng Qiao, and Edward Harrington, and Ashley Gusha, and Ahmad Al-Musa, and David H Sachs, and Mark Randolph, and Thomas J Bollenbach, and Christene A Huang
1 Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 2 Department of Pathology, Massachusetts General Hospital, Boston, MA. 3 Preclinical Research and Development Laboratory, Organogenesis Inc. Canton, MA. 4 Plastic Surgery Research Laboratory, Massachusetts General Hospital, Boston, MA.

Deficiency of autologous skin for reconstruction of severe wounds is a major problem in plastic surgery. Autologous substitutes can provide additional coverage, but due to the duration of production, treatment is significantly delayed. The allogeneic approach offers a potential of having an off-the-shelf solution for the immediate application. In this study, we assess the engraftment and immunogenicity of allogeneic bilayered bioengineered skin prepared by a self-assembly method. Bioengineered skin has the potential immunological advantage of lacking passenger leukocytes including antigen-presenting cells. The skin constructs were transplanted across major histocompatibility complex (MHC) barriers in a porcine animal model. Animals received a second grafting of the same skin construct 7 weeks after the first set of grafts together with MHC-matched constructs to assess for clinical sensitization. All alloconstructs successfully engrafted with histologic evidence of neovascularization by day 4. Complete cellular rejection and tissue loss occurred by day 8 for most grafts. After the second application, accelerated rejection (<4 days) took place with the development of swine MHC-specific cytotoxic alloantibody. These data demonstrate preclinically that self-assembled allogeneic constructs engraft and reject similar to allogeneic skin despite the absence of professional donor antigen-presenting cells.

UI MeSH Term Description Entries
D007518 Isoantibodies Antibodies from an individual that react with ISOANTIGENS of another individual of the same species. Alloantibodies
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000938 Antigen-Presenting Cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors. Accessory Cells, Immunologic,Antigen-Presenting Cell,Immunologic Accessory Cells,Accessory Cell, Immunologic,Cell, Immunologic Accessory,Cells, Immunologic Accessory,Immunologic Accessory Cell,Antigen Presenting Cell,Antigen Presenting Cells,Cell, Antigen-Presenting,Cells, Antigen-Presenting
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D013556 Swine, Miniature Genetically developed small pigs for use in biomedical research. There are several strains - Yucatan miniature, Sinclair miniature, and Minnesota miniature. Miniature Swine,Minipigs,Miniature Swines,Minipig,Swines, Miniature
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D016038 Skin Transplantation The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin. Dermatoplasty,Grafting, Skin,Transplantation, Skin,Dermatoplasties,Graftings, Skin,Skin Grafting,Skin Graftings,Skin Transplantations,Transplantations, Skin
D023822 Tissue Engineering Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures. Engineering, Tissue

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