The Edmonton Protocol and its more recent improvements are the product of incremental contributions made during the past 34 years. Paul E. Lacy first extracted islets from the rat pancreas with the enzyme collagenase, and used the islets to reverse diabetes in 1972.1 These tantalizing results in rodents left the distinct impression that islet-replacement therapy was a mere step away from the clinic. But extracting large numbers of healthy islets from the more fibrous human pancreas proved exceedingly difficult. Early attempts with unpurified pancreatic digests occasionally led to disaster.
Fatal portal vein thrombosis, portal hypertension, and disseminated intravascular coagulation were among the outcomes. Fortunately, islets have a lower osmotic density than the exocrine tissue, and that enabled purification on Ficoll gradients. Initially this required careful hand-layering in tubes, prolonged centrifugation, and then tedious aspiration of the purified islets. Scaling the technique from mouse to human required further innovation. Enter the ...
