Climov Mihail, Matar Abraham J, Farkash Evan A, Medeiros Erika, Qiao Jizeng, Harrington Edward, Gusha Ashley, Al-Musa Ahmad, Sachs David H, Randolph Mark, Bollenbach Thomas J, Huang Christene A
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.
Transplantation. 2016 Oct;100(10):2071-8. doi: 10.1097/TP.0000000000001353.
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.
严重伤口重建中自体皮肤不足是整形手术中的一个主要问题。自体替代物可提供额外的覆盖,但由于生产时间长,治疗会显著延迟。同种异体方法提供了一种现成解决方案以便立即应用的潜力。
在本研究中,我们评估通过自组装方法制备的同种异体双层生物工程皮肤的植入和免疫原性。生物工程皮肤具有缺乏包括抗原呈递细胞在内的过客白细胞的潜在免疫学优势。皮肤构建体在猪动物模型中跨越主要组织相容性复合体(MHC)屏障进行移植。在第一组移植7周后,动物接受相同皮肤构建体的第二次移植以及MHC匹配的构建体,以评估临床致敏情况。
到第4天时,所有异体构建体均成功植入,并有新血管形成的组织学证据。大多数移植物在第8天时发生完全细胞排斥和组织丢失。第二次应用后,随着猪MHC特异性细胞毒性同种异体抗体的产生,发生了加速排斥(<4天)。
这些数据在临床前证明,尽管没有专业的供体抗原呈递细胞,但自组装的同种异体构建体的植入和排斥与同种异体皮肤相似。