title: Long-term function of fish islet xenografts in mice by alginate encapsulation.
abstract: BACKGROUND
  Large, anatomically discrete pancreatic islets, Brockmann bodies (BBs), exist in certain teleost fish. When transplanted under the renal capsules of streptozotocin-diabetic athymic nude mice, BB grafts produce uniform normoglycemia for 50 days and mammalian-like glucose tolerance profiles; however, these very discordant islets reject in 7-8 days when transplanted into euthymic BALB/c mice.
  
  
  METHODS
  In the present study, BBs were mass harvested, minced into <1-mm tissue fragments, and encapsulated in alginate-based macrospheres (5 mm diameter) or noodles (0.5x3 cm). Nonencapsulated and encapsulated BB fragments were transplanted intraperitoneally into streptozotocin-diabetic (nonfasting blood glucose >400 mg/dl) nu/nu and BALB/c mice. Glucose levels were monitored at least 3 times a week.
  
  
  RESULTS
  Encapsulated BB grafts uniformly survived >50 days (10/10) or >100 days (3/3) in nu/nu recipients. The mean graft survival time was 27+/-13 days in BALB/c recipients (n=7). Daily intraperitoneal administration of 2.5 mg/kg 15-deoxyspergualin, in combination with encapsulation, resulted in uniform long-term BB graft function in BALB/c recipients (n=5). Similarly, long-term function was achieved in four of six BALB/c recipients with daily intraperitoneal administration of 10 mg/kg cyclosporine (two grafts failed after 39 and 45 days). Nonencapsulated BB grafts transplanted intraperitoneally into BALB/c or nu/nu recipients functioned for <7 days; immunosuppression alone did not permit graft survival in BALB/c recipients. In all cases of graft survival of >50 days, grafts were surgically removed from the peritoneal cavity, and blood sugar levels returned to a diabetic state within a few days. Historical sections of grafts, stained with hematoxylin and eosin and immunoperoxidase for insulin, showed viable, well-granulated BB tissue.
  
  
  CONCLUSIONS
  This study demonstrates that tilapia BBs are suitable for encapsulation and that encapsulated BBs can be made to function long term in diabetic mice.
authors.affiliation: Department of Pathology, Izaak Walton Killam-Grace Health Centre, Dalhousie University, Faculty of Medicine, Halifax, Nova Scotia, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: O'Hali
authors.forename: H
authors.initials: H
authors.lastname: Kearns
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
mesh_terms: D000464:Alginates; D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D004339:Drug Compounding; D006085:Graft Survival / Q000187:drug effects; D006146:Guanidines / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010473:Perciformes; D012086:Reoperation; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000502:physiology*
chemical_list: D000464:Alginates; D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus