*Purpose: AIPCs (Activated Islet Proliferating Cells), are a novel cell population from isolated human islets obtained using a simple culture protocol that can generate cells secreting both insulin and glucagon in response to secretagogues. Furthermore, AIPCs form Dithizone-positive islet-like cell clusters that respond to glucose stimulation and may represent de novo islets. When IV injected, AIPCs home and engraft in the pancreas and release insulin, and represent a viable option for cell transplantation for the treatment of diabetes. Herein we report the isolation of AIPCs from a biopsy from a patient with long-standing type 1 diabetes (56 years after diagnosis), and the generation of insulin secreting cells from non-insulin secreting pancreatic tissue.

*Methods: Biopsies of 1x1mm3 were obtained from the pancreas of a deceased organ donor with long standing (56 yrs) diabetes. Pancreas cold ischemia time was 9 hours and the organ was preserved in University of Wisconsin solution on ice. The biopsies were freshly cultured in the presence of culture medium containing IMG-i (a proprietary sequence) at 37ºC, 5% CO2.

*Results: After 12-15 days bioptic-derived cells were mobilized and began to adhere to the dish and to proliferate. During the subsequent 4-6 weeks, the adherent cells continued to proliferate, became confluent and kept multiplying, doubling every 3 days. Type 1 diabetes-derived AIPCs exhibited morphological similarities to AIPCs obtained from non-diabetic donors. Similarly, they formed islet-like cell clusters with size consistent with that of islets of Langerhans. Following glucose stimulation, secreted insulin was detected in the culture medium. Microarray mRNA profile of the cells confirmed gene profile compatible with a pancreatic endocrine islet cell population, with expression of insulin, and glucagon. Furthermore, these type 1 diabetes-derived AIPCs also expressed the pancreatic transcription factors PDX1, Nkx6, ngn3, NeuroD, and MafA and MafB, as well as the islet neogenesis factor nestin, the glucose transporter Glut-2, the secretory product of β-cells IAPP, and somatostatin which, is secreted by islet δ-cells. These findings suggest the ability of type 1 diabetes- derived AIPCs to generate insulin producing cells and carry all factors necessary for islet neogenesis.

*Conclusions: This study demonstrates that insulin producing cells can be obtained from culturing pancreatic biopsies from organ donors with long standing type 1 diabetes. This study provides the ground work and approach for the generation and treatment of type 1 diabetes in the setting of an autologous cell transplantation.

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