Developing a Stable Diabetic Model for Human Islet Assessment in the NOD-scid Mouse
Islet transplantation as a treatment for diabetes offers several potential advantages. These include normalization of glycemic control, a relatively non-traumatic transplant procedure and the potential for pretransplant procedures to eliminate the need for permanent immunosuppression (Ricordi et al. Diabetes 37:43, 1988). When successful, islet transplantation can keep patients insulin independent and normoglycemic for many years (Carroll et al. Transplantation 59:875–879, 1995; Kendall et al. Diabetes 45:257A, 1995; Robertson et al. Diabetes 50:47–50, 2001; Shapiro et al. Am J Transplant 3:296, 2003). However, islet grafts often suffer from immunological rejection and/or graft primary non-function (Bretzel et al. Exp Clin Endocrinol Diab 103:143–159, 1995). The non-function occurs immediately and is not affected by immunosuppressive drugs. Indeed, patients receiving islet autotransplants often experience reduced islet function below a level that allows them to remain insulin independent (Fontana et al. Transplant Proc 26:581, 1994), indicating that this problem is distinct from immunological rejection mediated by adaptive immunity. Primary non-function from nonspecific inflammatory response appears to be a problem that has impaired the success of islet transplantation in humans (Stevens et al. Transplant Proc 26:692, 1994).
The study of in vivo (biological) islet function without interference from immune reactions and immunosuppressive drugs has proven difficult due to a lack of good animal models. We have developed a novel NOD-scid mouse, cellular xenograft model for used in the study of human islets. This model is uniquely suited for the study of islet viability because the mouse not only bears the scid defect, but also an impairment of the animals innate immunity.
KeywordsCellular xenograft model Diabetes Glucotoxicity Immunosupression Islet transplantation Mouse model Streptozotocin
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