P-192

Endothelial cells promote pancreatic stem cell activation during islet regeneration

S.D. Rivas-Carrillo¹, J. Kanamune², A. Daneri-Navarro¹, J. D. Rivas-Carrillo^1
1 University of Guadalajara, Dept of Physiology, Labs of Immunology and Transplant, Guadalajara, Mexico; ² Kyoto University Hospital, Dept of Transplant Surgery, Pancreas and Islet Transplantation Unit, Kyoto, Japan

Objectives:Diabetes is the clinical consequence of the loss of the majority of the ? cell population and failure to regenerate new pancreatic ?-cells. The current therapies based on ? cell replacement have failed to achieve ? cell renewal and thus, long-term insulin freedom. We have hypothesized that early rejection of endothelial within the islet grafts may seriously hampered islet regeneration of both native and islet grafts.

Methods: In the present study, we analyzed the role of endothelial cells in the activation of pancreatic stem cells during islet regeneration. Mice were pretreated with or without endothelial pharmacological ablation of endothelial cells, followed by an acute ? cell injury using a single intraperitoneal injection of streptozotocin.

We performed a comparative morphometric analyses within the recovered pancreata on days 3^rd, 7^th, 10^th and 30^th after streptozotocin injury, and thus stained for representative cell types, ? cell, endothelial and stem cells co-stained with BrdU. Blood glucose levels were measured continuously after injury to monitor the capacity of metabolic control.

Results: Morphometric analyses revealed an increased number over time of cells stained with a stem cell marker and BrdU marker in animals only injured with streptozotocin but no endothelial ablation. Notably, on day 10^th stem cell marker dramatically decrease nearly basal levels, and instead numerous insulin-positive cells appeared. Intact vessels with cobblestone-shaped endothelial were observed in direct proportion with better outcomes, in both morphometric and metabolic parameters. In contrast, fewer insulin positive cells were found on pancreata, which were ablated ofendothelial cells, and showed an extensive collapse of the entire endocrine functions.

Conclusions: We have found that endothelial promote stem cell proliferation and islet regeneration after ? cell insult. We believe that preservation of endothelial cells may positively affect the process of pancreatic regeneration.

P-192

Endothelial cells promote pancreatic stem cell activation during islet regeneration

S.D. Rivas-Carrillo¹, J. Kanamune², A. Daneri-Navarro¹, J. D. Rivas-Carrillo^1
1 University of Guadalajara, Dept of Physiology, Labs of Immunology and Transplant, Guadalajara, Mexico; ² Kyoto University Hospital, Dept of Transplant Surgery, Pancreas and Islet Transplantation Unit, Kyoto, Japan

Objectives:Diabetes is the clinical consequence of the loss of the majority of the ? cell population and failure to regenerate new pancreatic ?-cells. The current therapies based on ? cell replacement have failed to achieve ? cell renewal and thus, long-term insulin freedom. We have hypothesized that early rejection of endothelial within the islet grafts may seriously hampered islet regeneration of both native and islet grafts.

Methods: In the present study, we analyzed the role of endothelial cells in the activation of pancreatic stem cells during islet regeneration. Mice were pretreated with or without endothelial pharmacological ablation of endothelial cells, followed by an acute ? cell injury using a single intraperitoneal injection of streptozotocin.

We performed a comparative morphometric analyses within the recovered pancreata on days 3^rd, 7^th, 10^th and 30^th after streptozotocin injury, and thus stained for representative cell types, ? cell, endothelial and stem cells co-stained with BrdU. Blood glucose levels were measured continuously after injury to monitor the capacity of metabolic control.

Results: Morphometric analyses revealed an increased number over time of cells stained with a stem cell marker and BrdU marker in animals only injured with streptozotocin but no endothelial ablation. Notably, on day 10^th stem cell marker dramatically decrease nearly basal levels, and instead numerous insulin-positive cells appeared. Intact vessels with cobblestone-shaped endothelial were observed in direct proportion with better outcomes, in both morphometric and metabolic parameters. In contrast, fewer insulin positive cells were found on pancreata, which were ablated ofendothelial cells, and showed an extensive collapse of the entire endocrine functions.

Conclusions: We have found that endothelial promote stem cell proliferation and islet regeneration after ? cell insult. We believe that preservation of endothelial cells may positively affect the process of pancreatic regeneration.