Human islet implantation (the problems and the promise).

Compton, Frederick J (1985). Human islet implantation (the problems and the promise). PhD thesis The Open University.



The discovery of insulin was a mile stone in the treatment of diabetes. For most diabetics however, the development of the secondary complications of the disease are often fatal and the cause and prevention of these secondary lesions remains the outstanding problem in the treatment of the disease.

Islet cell transplantation as a total cure for the disease was proposed over 80 years ago. Islet implantation in rodents is now a safe and reliable method of reversing the metabolic derangements and preventing diabetic lesions in experimental animals. The problem of isolating sufficient islets from the human pancreas and in avoiding the immune tissue rejection phenomena have so far precluded its successful application in man.

Enzymes of defined activity were used to achieve dissaggregation of the human pancreas. A periperfusion system was developed for evaluating the dynamic aspects of insulin release both from normal and dispersed pancreatic tissue. This allowed critical aspects in the technique of tissue disaggregation to be examined and improved, such that in excess of 60% of the initial islet function could be recovered following disaggregation.

Implantion of this crude pancreatic disaggregate in the canine model resulted in uncontrolled fluctuations in blood glucose levels, a massive bleeding diathesis and hepatic trauma, indicating the need for purer islet preparations.

Attachment of islets to a collagen substrate was found to allow recovery of islets as an essentially pure preparation. Tissue culture techniques were used to confirm the viability of pancreatic islets isolated in this way.

Finally the problem of abrogating the immune tissue rejection phenomena was investigated across a discordant xenogeneic histocorapatability barrier. The imraunogenicity of human islets was shown to be altered following tissue culture of 28 days such that survival of 3 months was achieved in an immunocorapetant host.

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