An isolated venous sac as a novel site for cell therapy in diabetes mellitus

Zurab Kakabadze, Koba Shanava, Camillo Ricordi, A. M James Shapiro, Sanjeev Gupta, Ekaterine Berishvili

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalTransplantation
Volume94
Issue number4
DOIs
StatePublished - Aug 27 2012

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Cell- and Tissue-Based Therapy
Diabetes Mellitus
Islets of Langerhans Transplantation
Islets of Langerhans
Hyperglycemia
Vasa Vasorum
Experimental Diabetes Mellitus
Microcirculation
Portal Vein
Type 1 Diabetes Mellitus
Blood Vessels
Drainage
Veins
Histology
Insulin
Transplants
Recurrence
Injections

Keywords

  • Intravascular transplantation
  • Islets
  • Pancreas

ASJC Scopus subject areas

  • Transplantation

Cite this

Kakabadze, Z., Shanava, K., Ricordi, C., Shapiro, A. M. J., Gupta, S., & Berishvili, E. (2012). An isolated venous sac as a novel site for cell therapy in diabetes mellitus. Transplantation, 94(4), 319-324. https://doi.org/10.1097/TP.0b013e31825e4a83

An isolated venous sac as a novel site for cell therapy in diabetes mellitus. / Kakabadze, Zurab; Shanava, Koba; Ricordi, Camillo; Shapiro, A. M James; Gupta, Sanjeev; Berishvili, Ekaterine.

In: Transplantation, Vol. 94, No. 4, 27.08.2012, p. 319-324.

Research output: Contribution to journalArticle

Kakabadze, Z, Shanava, K, Ricordi, C, Shapiro, AMJ, Gupta, S & Berishvili, E 2012, 'An isolated venous sac as a novel site for cell therapy in diabetes mellitus', Transplantation, vol. 94, no. 4, pp. 319-324. https://doi.org/10.1097/TP.0b013e31825e4a83
Kakabadze, Zurab ; Shanava, Koba ; Ricordi, Camillo ; Shapiro, A. M James ; Gupta, Sanjeev ; Berishvili, Ekaterine. / An isolated venous sac as a novel site for cell therapy in diabetes mellitus. In: Transplantation. 2012 ; Vol. 94, No. 4. pp. 319-324.
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