Tilapia Brockmann Bodies: an inexpensive, simple model for discordant islet xenotransplantation.
Brockmann bodies (BBs), large anatomically discrete islet organs found in some teleost fish, are much more easily harvested than pancreatic islets from mammalian donor sources. Tilapia islets, when transplanted into streptozotocin-diabetic athymic nude mice, will produce long-term normoglycemia and mammalian-like glucose tolerance profiles. Our laboratory has used tilapia BBs as an inexpensive model for studying islet xenograft rejection between discordant species. When transplanted into immunocompetent diabetic mice, tilapia BBs reject in roughly 7-8 days. Results to date suggest that tilapia islets are very immunogenic and that encapsulation is necessary to achieve long-term function in euthymic recipients. Continuous, high-dose immunosuppression using 15-DSG is also effective but causes lethal bone marrow suppression. Less aggressive immunosuppression regimens have achieved only modest prolongation of mean graft survival time. Thus far, immunomodulation techniques and transplantation into immune-privileged sites have been ineffective at prolonging graft survival. Tilapia islets currently represent an excellent, inexpensive donor source for discordant islet xenotransplantation studies. In the not distant future, encapsulated islets harvested from transgenic tilapia bearing humanized tilapia insulin genes may also play a role in establishing clinical islet xenotransplantation as a useful treatment modality for type I diabetes mellitus.
Wright
J R
JR
Department of Pathology, Izaak Walton Killam-Grace Health Centre, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada. jwright@iwkgrace.ns.ca
Yang
H
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D017210:Tilapia; D014183:Transplantation, Heterologous / Q000276:immunology
D007166:Immunosuppressive Agents