title: Juvenile porcine islets can restore euglycemia in diabetic athymic nude mice after xenotransplantation.
abstract: BACKGROUND
  Porcine islet xenotransplantation has been demonstrated in many animal studies to cure experimentally induced diabetes. However, several issues currently impede the translation of porcine islet xenotransplantation to sustained insulin independence clinically. Although adult pigs have mature islets that secrete insulin in response to a glucose challenge, and are physiologically similar to humans, there are logistical considerations with adult porcine tissue that are not present with juvenile porcine tissue. To circumvent these issues, we have identified 18- to 21-day-old preweaned juvenile pigs as islet donors as we have previously demonstrated superior islet yields and function from juvenile pigs using our islet isolation protocols.
  
  
  METHODS
  We evaluated the efficacy of islets isolated from 18- to 24-day-old Yorkshire swine in vitro using a standard glucose-stimulated insulin response assay, and in vivo after xenotransplantation under the kidney capsule of streptozotocin-induced 8- to 10-week-old male athymic nude mice. The mice were monitored for a period of 60 days after transplantation, after which the grafts were explanted and analyzed.
  
  
  RESULTS
  Diabetic athymic nude mice transplanted with 1500 to 3000 islet equivalents (IEq) of islets achieved sustained normoglycemia for up to 60 days after islet transplantation. When the grafts were explanted with the kidney, a rapid return to hyperglycemia was observed.
  
  
  CONCLUSIONS
  Efficacy and dose-titration studies evaluating these islets in immunocompetent and nonobese diabetic mouse models are underway. The results of these studies will permit application for nonhuman primate and pivotal clinical trials in human diabetic patients in the near future.
authors: 1 Department of Surgery, University of California Irvine, Orange, CA. 2 Department of Biomedical Engineering, University of California, Irvine, Irvine, CA.
authors: Rahul
authors: R
authors: Krishnan
authors: Brian
authors: B
authors: Buder
authors: Michael
authors: M
authors: Alexander
authors: Clarence E
authors: CE
authors: Foster
authors: Jonathan Rt
authors: JR
authors: Lakey
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D006085:Graft Survival; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007668:Kidney / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008819:Mice, Nude; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function; D013552:Swine; D013997:Time Factors; D046509:Tissue Culture Techniques; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers; D001786:Blood Glucose