Fetal pancreas as a donor organ

Abstract

Abstract The use of the fetal pancreas as a donor organ for the treatment of diabetes has been explored in the rat and currently is being tried in minipigs. Growth and development of a fetal pancreas under the kidney capsule of a diabetic rat is sufficient to completely reverse streptozotocin diabetes; the organ contains 20–25% of the insulin content of a normal adult pancreas. The fetal pancreas grows and develops most fully in normoglycemic environment. Cryopreservation results in nearly complete survival of the pancreas and provides time for tissue and blood typing and testing for compatibility of donor and recipient lymphocytes using the Mixed Leucocyte Reaction. These methods have been developed in human systems. Removal of the pancreas from the fetus and transplantation prior to a critical period of exocrine development (18 days in the rat, 55 in the pig) are followed by atrophy of exocrine elements and a pure endocrine organ results. This obviates the problem of exocrine enzymes. Venous drainage of insulin from the transplanted pancreas into the liver provides the most effective response when the supply of insulin is limited. Metabolic studies in successfully‐transplanted rats indicate complete reversal of the diabetic state to normal. These include blood glucose and insulin levels and responses to stimuli, the activity levels of 6 enzymes in the liver, glucagon levels, and the response to arginine stimulation and glucose metabolism during and after pregnancy . Methods that have been used to prevent rejection, all of which have been partially effective, include donor liver pretreatment and short‐term immunosuppression, total lymphoid irradiation combined with donor bone marrow, and treatment of the donor organ to eliminate immune cells by digestion and culture. Additional research will be required to develop an effective and safe method for prevention of allograft rejection in the minipig prior to application to diabetic humans .