P-238

Impact of liver microfragments and islet co-transplantation on the streptozotocine induced diabetes in rats

Z. Kakabadze¹, E. Berishvili¹, G. Shatirishvili², G. Loladze², K. Mardaleishvili^2
1 Tbilisi State Medical University, Tbilisi, Georgia; ² Cell Therapy and Technology Center, Tbilisi, Georgia

Objective: We hypothesized that vascularized intestinalsegment preliminary ablated from mucosa would provide opportunities for revascularizationof transplanted cells. Our recent studies have shown that isolated smallintestinal segments permitted the engrafted islets to maintain functions in thelong-term. The aim of this study was to show whether incorporation of liverfragments would be helpful in the survival and organization of pancreaticislets by providing synergistic support.

Methods: Male Lewis diabetic rats were rendered byintraperitoneal injection of streptozotocin. One group of rats (n=20) received 500syngenic pancreatic islets along with liver fragments in small intestinesegments. The animals of the second group (n=20) received intraportal infusionof 500 islets. The animals of the third group (n=20) received 500 pancreaticislets beneath kidney capsule. Blood glucose levels were monitored andintraperitoneal glucose tolerance tests carried out. Histological assessmentfor insulin, glucagon, von Willebrand factor (vWF) was performed. The reversetranscription-polymerase chain reaction was performed to analize the expressionof insulin, glucagon, somatostatin, Glut1, PDX1, PAX6, TGF?, TGFß, bFGF andVEGF.

Results: In all diabetic animals of I and II groupsblood glucose levels returned to normoglycemic ranges within 20 days. Indiabetic rats of I and II groups, glucose challenge on day 58 showed rapidreturn to normoglycemia. The overall morphological structure of transplanted isletsand liver fragments appeared to be well preserved over up to 6 month. Insulin andglucagon were expressed in transplanted islets throughout the observationperiod. The PCR analysis showed that expression of multiple growth factors wasgenerally retained in the transplanted islet-liver co-transplants, including betacell transcription factors and hormones.

Conclusions: These encouraging features of the isolatedintestinal segment indicate that such a system is a significant alternative toaddress biological mechanisms and clinical applications.

P-238

Impact of liver microfragments and islet co-transplantation on the streptozotocine induced diabetes in rats

Z. Kakabadze¹, E. Berishvili¹, G. Shatirishvili², G. Loladze², K. Mardaleishvili^2
1 Tbilisi State Medical University, Tbilisi, Georgia; ² Cell Therapy and Technology Center, Tbilisi, Georgia

Objective: We hypothesized that vascularized intestinalsegment preliminary ablated from mucosa would provide opportunities for revascularizationof transplanted cells. Our recent studies have shown that isolated smallintestinal segments permitted the engrafted islets to maintain functions in thelong-term. The aim of this study was to show whether incorporation of liverfragments would be helpful in the survival and organization of pancreaticislets by providing synergistic support.

Methods: Male Lewis diabetic rats were rendered byintraperitoneal injection of streptozotocin. One group of rats (n=20) received 500syngenic pancreatic islets along with liver fragments in small intestinesegments. The animals of the second group (n=20) received intraportal infusionof 500 islets. The animals of the third group (n=20) received 500 pancreaticislets beneath kidney capsule. Blood glucose levels were monitored andintraperitoneal glucose tolerance tests carried out. Histological assessmentfor insulin, glucagon, von Willebrand factor (vWF) was performed. The reversetranscription-polymerase chain reaction was performed to analize the expressionof insulin, glucagon, somatostatin, Glut1, PDX1, PAX6, TGF?, TGFß, bFGF andVEGF.

Results: In all diabetic animals of I and II groupsblood glucose levels returned to normoglycemic ranges within 20 days. Indiabetic rats of I and II groups, glucose challenge on day 58 showed rapidreturn to normoglycemia. The overall morphological structure of transplanted isletsand liver fragments appeared to be well preserved over up to 6 month. Insulin andglucagon were expressed in transplanted islets throughout the observationperiod. The PCR analysis showed that expression of multiple growth factors wasgenerally retained in the transplanted islet-liver co-transplants, including betacell transcription factors and hormones.

Conclusions: These encouraging features of the isolatedintestinal segment indicate that such a system is a significant alternative toaddress biological mechanisms and clinical applications.