175 Potential Application of Neonatal Porcine Islets as Treatment for Type 1 Diabetes: A Review GINA R. RAYAT, RAY V. RAJOTTE, AND GREGORY S. KORBUTT a Department of Surgery, Surgical-Medical Research Institute, University of Alberta, Edmonton, Canada ABSTRACT: Islet transplantation has been shown to be a viable option for treating patients with type 1 diabetes. However, widespread clinical applica- tion of this treatment will necessitate an alternative source of insulin-produc- ing tissue. Porcine pancreata may be a potential source of islets since pigs are inexpensive, readily available, and exhibit morphological and physiological characteristics comparable to humans. Recently, we developed a simple, stan- dardized procedure for isolating large numbers of neonatal porcine islets with a reproducible and defined cellular composition. Following nine days of in vitro culture, tissue from one neonatal pig pancreas yielded approximately 50,000 is- let cell aggregates, consisting of primarily epithelial cells (57%) and pancreatic endocrine cells (35%). In addition, neonatal porcine islets were responsive to glucose challenge in vitro and were capable of correcting hyperglycemia in al- loxan-induced diabetic nude mice. Although neonatal porcine islets constitute an attractive alternative source of insulin-producing tissue for clinical trans- plantation, many aspects such as the immunological responses to these tissue and the latent period (2 to 8 weeks) between transplantation of these islets and the reversal of hyperglycemia need further investigation. This article discusses these issues and presents possible solutions to problems that may hinder the potential application of neonatal porcine islets for transplantation into patients with type 1 diabetes. INTRODUCTION The discovery of insulin at the University of Toronto in 1922 was one of the most dramatic events in the history of the treatment of type 1 diabetes. 1 Insulin therapy has improved the quality of life and extended the life expectancy of patients with di- abetes; however, this current mode of treatment does not protect diabetic patients from episodes of abnormally high blood glucose levels, which can lead to chronic complications unless intensive insulin therapy is used. The main focus of diabetes research has been to develop better methods of treatment which can prevent the long- term complications of this disease. Endocrine replacement by islet transplantation is an attractive alternative treatment because it offers a physiological means for precise restoration of euglycemia in patients with type 1 diabetes. Over the past 16 years, significant advances have been made in the number and purity of islets that can be harvested from the human pancreas. 2–7 Reports of both a Author for correspondence: Surgical-Medical Research Institute, 1074 Dentistry/Pharmacy Building, University of Alberta, Edmonton, Alberta T6G 2N8 Canada; 780-492-4657 (voice); 780-492-1627 (fax); korbutt@gpu.srv.ualberta.ca (e-mail).