(taken directly from the application): The objectives and Specific Aims are to provide mouse, rat, and porcine islet tissue to the participants of the PPG for their in vitro studies on immune rejection mechanisms and islet function, for gene transfer experiments, and for transplantation. In addition, the techniques of islet cell transplantation will be taught to investigators and their lab members as required. Background: This PPG is focused upon islet transplantation, with the expectation that porcine islets will be transplanted into humans with IDDM. Because of the serious shortage of human islet tissue, it will probably be necessary to use islets from other species. For a variety of reasons, including ready availability, pigs seem particularly well suited for xenografting. Therefore, both adult porcine islets and porcine neonatal pancreatic cell clusters (NPCCs) will be made available to the participants of the PPG. NPCCs seem particularly promising because they are hardy, have impressive capacity for growth and differentiation, and seem particularly well suited for genetic modification. Rat and mouse islets will also be supplied to the four Projects. Although the goal of this work is to transplant genetically modified pig islets into primates, a large amount of background work must first be carried out with rodent islets, which have proved to be the most widely used models for the study of islet transplantation immunology, as well as islet physiology and cell biology.

Project Start
2001-12-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
5
Fiscal Year
2002
Total Cost
$211,312
Indirect Cost
Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215
Koulmanda, M; Qipo, A; Fan, Z et al. (2012) Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term triple therapy. Am J Transplant 12:1296-302
Laybutt, D R; Hawkins, Y C; Lock, J et al. (2007) Influence of diabetes on the loss of beta cell differentiation after islet transplantation in rats. Diabetologia 50:2117-25
Koulmanda, M; Smith, R N; Qipo, A et al. (2006) Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based therapy: nonimmunologic graft failure? Am J Transplant 6:687-96
Koulmanda, Maria; Laufer, Terri M; Auchincloss Jr, Hugh et al. (2004) Prolonged survival of fetal pig islet xenografts in mice lacking the capacity for an indirect response. Xenotransplantation 11:525-30
Koulmanda, M; Qipo, A; Chebrolu, S et al. (2003) The effect of low versus high dose of streptozotocin in cynomolgus monkeys (Macaca fascilularis). Am J Transplant 3:267-72
Omer, Abdulkadir; Keegan, Mitchell; Czismadia, Eva et al. (2003) Macrophage depletion improves survival of porcine neonatal pancreatic cell clusters contained in alginate macrocapsules transplanted into rats. Xenotransplantation 10:240-51
Koulmanda, Maria; Qipo, Andi; Smith, R Neal et al. (2003) Pig islet xenografts are resistant to autoimmune destruction by non-obese diabetic recipients after anti-CD4 treatment. Xenotransplantation 10:178-84
Grey, Shane T; Longo, Christopher; Shukri, Tala et al. (2003) Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. J Immunol 170:6250-6
Omer, Abdulkadir; Duvivier-Kali, Valerie F; Trivedi, Nitin et al. (2003) Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice. Diabetes 52:69-75
Koulmanda, M; Qipo, A; Auchincloss Jr, H et al. (2003) Effects of streptozotocin on autoimmune diabetes in NOD mice. Clin Exp Immunol 134:210-6

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