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TRANSLATIONAL PHYSIOLOGY

Islet cell engraftment and control of diabetes in rats after transplantation of pig pancreatic anlagen

Renal Division, Departments of ¹Medicine, ²Comparative Medicine, and ³Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

Submitted 2 October 2003 ; accepted in final form 12 December 2003

The insufficient supply of tissue, loss posttransplantation, and limited potential for expansion of -cells restrict the use of islet allotransplantation for diabetes. A way to overcome the supply and expansion problems is to xenotransplant embryonic tissue. We have shown that whole rat pancreatic anlagen isotransplanted into the omentum of rats, or xenotransplanted into costimulatory blocked mice, undergo growth and differentiate into islets surrounded by stoma without exocrine tissue. Isotransplants normalize glucose tolerance in diabetic hosts. Here, we show that embryonic day 29 porcine pancreas transplanted into the omentum of adult diabetic rats undergoes endocrine tissue differentiation over 20 wk and normalizes body weights and glucose tolerance. Unlike rat-to-rodent transplants, individual - and -cells engraft without a stromal component, and no immunosuppression is required for pig-to-rat transplants. Herein is described a novel means to effect the xenotransplantation of individual islet cells across a highly disparate barrier.

-cell; -cell; insulin; xenotransplantation

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