Biohybrid Artificial Pancreas Long-Term Insulin Secretion by Devices Seeded with Canine Islets

Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture medium 199 containing 300 mg/dl glucose. Insulin secretion fell during the first 1–2 days of culture from approximately 18 to 6 U/day. After 3–4 wk of perfusion, however, there was a gradual rise in insulin output that reached >15 U/day after 7 wk. Insulin output eventually stabilized at 18–20 U/day. Two of these devices were studied for 80 and 86 days, respectively, and continued to secrete these same amounts of insulin. Glucose-induced insulin release was studied after 1 and 4 wk of culture and was well preserved.