Immunopathologic Studies

核心A将执行该计划项目中的所有病理组织研究。该中心将由哈佛/马萨诸塞州总医院的本杰明·卡斯特尔曼病理学特聘教授、医学博士罗伯特·B·科尔文领导。他是国际公认的移植病理学研究人员，过去曾与其他研究人员广泛合作。病理学副教授R.Neal Smith和外科(免疫学)助理教授Sandro Alessandrini将加入这项工作，前者在胰岛移植病理学方面拥有专业知识，后者在内皮激活途径、Treg和树突状细胞方面有经验。这些研究将在马萨诸塞州综合医院(Thier 8)的免疫病理学研究实验室进行。不会使用胚胎干细胞。 将使用的技术包括常规组织学、免疫组织化学、免疫荧光和电子显微镜。免疫过氧化物酶技术和一组单抗将区分浸润性细胞类型(TJeff、Treg、Breg等)、黏附和细胞因子分子和受体、补体沉积(C4D)和内皮激活标志物(例如PERK)。全幻灯片数字扫描和形态测量将加强对原位过程的分析。病理学结果将与项目中所做的功能和分子研究相关联。此外，将对所有动物进行全面尸检，并按要求对所有主要器官的样本进行常规和特殊技术分析。

Core A will perform all pathology tissue studies in this program project. The Core will be led by Robert B. Colvin, M.D., who is the Benjamin Castleman Distinguished Professor of Pathology at Harvard/Massachusetts General Hospital. He is an internationally recognized investigator in transplantation pathology and has collaborated extensively in the past with the other investigators. He will be joined in this effort by R. Neal Smith, Associate Professor of Pathology, who has expertise in islet transplantation pathology and Sandro Alessandrini, Assistant Professor of Surgery (Immunology), who has experience with endothelial activation pathways, Treg and dendritic cells. The studies will be performed in the Immunopathology Research Laboratory at the Massachusetts General Hospital (Thier 8). No embryonic stem cells will be used. The techniques that will be utilized include routine histology, immunohistochemistry, immunofluorescence, and electron microscopy. Immunoperoxidase techniques with a panel of mAbs will distinguish the infiltrating cell types (Teff, Treg, Breg, et al), adhesion and cytokine molecules and receptors, complement deposition (C4d), and endothelial activation markers (e.g., pERK). Analysis ofthe in situ processes will be enhanced by whole slide digital scans and morphometry. The pathology results will be correlated with functional and molecular studies done in the projects. In addition, complete necropsies will be done on all animals, with samples from all major organs analyzed by routine and special techniques as indicated.