An isolated venous sac as a novel site for cell therapy in diabetes mellitus.
BACKGROUND
Transplanting pancreatic islets is of significant interest for type 1 diabetes mellitus. After intraportal injection of islets, inferior engraftment and eventual loss of transplanted islets constitute major limitations. Therefore, alternative approaches will be helpful. Here, we evaluated in animals whether an isolated venous sac would support survival of transplanted islets, along with correction of hyperglycemia.


METHODS
Pancreatic islets isolated from adult Lewis rats were transplanted either into an isolated venous sac made from lumbar vein or into the portal vein of syngeneic rats. The integrity and vascular organization of the venous sac was determined by studies of the local microcirculation. The engraftment, survival, and function of transplanted islets were analyzed by histology, including endocrine function in situ and by glycemic control in rats with streptozotocin-induced diabetes.


RESULTS
Transplanted islets showed normal morphology with insulin expression in isolated venous sac during the long term. Transplanted islets received blood supply from vasa vasorum and had access to drainage through venous tributaries in the venous sac. This resulted in restoration of euglycemia in diabetic rats. Removal of islet graft-bearing venous sac in diabetic rats led to recurrence of hyperglycemia. By contrast, euglycemia was not restored in rats treated by intraportal transplantation of islets.


CONCLUSIONS
We demonstrated that pancreatic islets successfully engrafted and functioned in the isolated venous sac with ability to restore euglycemia in diabetic rats. Therefore, the isolated venous sac offers a new site for transplantation of pancreatic islets. This would be clinically beneficial as an alternative to intrahepatic islet transplantation.
Department of Clinical Anatomy, Tbilisi State Medical University, and Division of Cell Transplantation, Georgian National Institute of Medical Research, DRI Federation, Tbilisi, GA, USA.
Zurab
Z
Kakabadze
Koba
K
Shanava
Camillo
C
Ricordi
A M James
AM
Shapiro
Sanjeev
S
Gupta
Ekaterine
E
Berishvili
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005951:Glucose Tolerance Test; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000401:mortality; D008297:Male; D011169:Portal Vein / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D012501:Saphenous Vein / Q000503:physiopathology; D013311:Streptozocin
D013311:Streptozocin