title: Xenogeneic milieu markedly remodels endocrine cell populations after transplantation of fish islets into streptozotocin-diabetic nude mice.
abstract: It is unknown whether irrelevant foreign endocrine products secreted by xenografts would be biologically active and potentially harmful to recipients; even if entirely inert, continuous production might result in harmful circulating antigen-antibody complexes. We examined the fate of such a product using a fish (tilapia)-to-mouse islet xenograft model. Teleost fish islets, like mammalian islets, are composed primarily of cells producing insulin, glucagon or somatostatin; however, teleost fish have two different populations of somatostatin (SST) producing delta cells, one producing SST-14, a 14 amino acid SST identical to mammalian SST, which is derived from the pre-proSST-I gene which is present in all vertebrates, and the other a "large" (i.e. 22 to 28 amino acid) SST derived from a pre-proSST-II gene, which is not found in mammals. In contrast to 'large' SST, which has no mammalian homolog, teleost fish insulins, glucagons and SST-14 exhibit significant biological activity in mammals. Tilapia islets were transplanted under the kidney capsules of streptozotocin-diabetic nude mice, and mice with functioning grafts were killed at various times after transplantation. Serial sections of graft-bearing kidneys were stained by immunoperoxidase for insulin, SST-14, SST-25 and glucagon positive cells, and the areas of each cell type in the graft were measured using image analysis. Sections of untransplanted tilapia islets (both in situ and after harvest/culture) were also immunostained and measured as controls. Xenotransplantation of fish islets into diabetic nude mice resulted in the rapid degeneration and near total loss of SST-25+ cells, as well as a marked redistribution of the proportions of the remaining endocrine cell types. The proportions of cell types in the grafts gradually changed from a piscine pattern to that of mammalian islets.
authors.affiliation: Department of Pathology, IWK Health Center, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Morrison
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Jazaeri
authors.forename: Janet
authors.initials: J
authors.lastname: Tam
authors.forename: Erika M
authors.initials: EM
authors.lastname: Plisetskaya
authors.forename: James R
authors.initials: JR
authors.lastname: Wright
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005934:Glucagon / Q000032:analysis; D006085:Graft Survival / Q000502:physiology*; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000601:surgery; D008297:Male; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D013004:Somatostatin / Q000032:analysis; D017210:Tilapia; D014183:Transplantation, Heterologous
chemical_list: D007328:Insulin; D013004:Somatostatin; C026568:somatostatin 25; D005934:Glucagon