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FETAL PANCREAS TRANSPLANTATION IN MINIATURE SWINE: I. DEVELOPMENTAL CHARACTERISTICS OF FETAL PIG PANCREASES

The genetically defined miniature pig developed by Sachs et al. was selected as a large animal model to test the feasibility of fetal pancreas transplants for reversal of insulin-dependent diabetes. In order to test our approach, the first key was to characterize the development of the pig pancreas tissues throughout fetal life. Pancreas samples were obtained from 102 farm pig fetuses ranging in age from 35–110 days and from 39 minipig fetuses removed by Caesarean section from 5 timed-pregnant sows between 33 and 73 days after conception. The development of the endocrine and exocrine pancreases were examined by immunobiochemical assays of insulin, chymotrypsinogen, and trypsinogen. Light and electron microscopic examination of pancreases from the critical fetal ages (35–55 days) were used to confirm the above results. Insulin was already present at day 33 and increased rapidly till birth (day 114: 2.2 U/pancreas). Chymotrypsinogen activity was first detected at day 43 and trypsinogen activity at days 49–50. Enzyme content increased rapidly till days 65–70 and then more gradually until birth. Morphological development of exocrine cell granules conformed to the above results. The results clearly demonstrated in the pancreas of a larger mammal, the pig, that the endocrine elements mature prior to the exocrine system. Thus, as we found in rats, pig fetal pancreas also has this advantage as a donor tissue for transplantation. An appropriate fetal age for pig donors is estimated to be between 45 and 50 days.