Correction of diabetes mellitus by transplanting minimal mass of syngeneic islets into vascularized small intestinal segment

Z. Kakabadze, S. Gupta, A. Pileggi, Ruth Molano, Camillo Ricordi, G. Shatirishvili, G. Loladze, K. Mardaleishvili, M. Kakabadze, E. Berishvili

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Transplantation of mature islets into portal vein has been most effective thus far, although attrition of transplanted islets constitutes a major limitation, and alternative approaches are required. We analyzed the mechanisms by which islets engrafted, vascularized and functioned over the long term in the small intestinal submucosa. To determine engraftment, survival and function, 350 syngenic islets were transplanted into either intestinal segments or portal vein of diabetic rats. Islet reorganization, vascularization and function were analyzed by histological analysis, RT-PCR analysis as well as glycemic control over up to 1 year. Transplantation of syngeneic islets in marginal numbers successfully restored normoglycemia in diabetic rats. Transplantation of semi-pure islet preparation did not impair their engraftment, vascularization and function. Islets were morphologically intact and expressed insulin as well as glucagon over the year. Expression of angiogenic genes permitted revascularization of transplanted islets. We identified the expression of transcription factors required for maintenance of beta cells. These studies demonstrated that marginal mass of transplanted islets was sufficient to restore euglycemia in streptozotocin-treated rats. These superior results were obtained despite use of an impure preparation of islets in animals with small intestinal segment. Our findings will help advance new horizons for cell therapy in patients with diabetes. Syngeneic transplantation of minimal mass pancreatic islet grafts into an isolated venous sac in diabetic rats is followed by successful engraftment and function with restoration of euglycemia.

Original languageEnglish
Pages (from-to)2550-2557
Number of pages8
JournalAmerican Journal of Transplantation
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Diabetes Mellitus
Isogeneic Transplantation
Islets of Langerhans Transplantation
Portal Vein
Streptozocin
Cell- and Tissue-Based Therapy
Glucagon
Islets of Langerhans
Transcription Factors
Transplantation
Maintenance
Insulin
Transplants
Gene Expression
Polymerase Chain Reaction
Survival

Keywords

  • Islets
  • pancreas
  • portal vein
  • small intestine
  • transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Correction of diabetes mellitus by transplanting minimal mass of syngeneic islets into vascularized small intestinal segment. / Kakabadze, Z.; Gupta, S.; Pileggi, A.; Molano, Ruth; Ricordi, Camillo; Shatirishvili, G.; Loladze, G.; Mardaleishvili, K.; Kakabadze, M.; Berishvili, E.

In: American Journal of Transplantation, Vol. 13, No. 10, 01.10.2013, p. 2550-2557.

Research output: Contribution to journalArticle

Kakabadze, Z, Gupta, S, Pileggi, A, Molano, R, Ricordi, C, Shatirishvili, G, Loladze, G, Mardaleishvili, K, Kakabadze, M & Berishvili, E 2013, 'Correction of diabetes mellitus by transplanting minimal mass of syngeneic islets into vascularized small intestinal segment', American Journal of Transplantation, vol. 13, no. 10, pp. 2550-2557. https://doi.org/10.1111/ajt.12412
Kakabadze, Z. ; Gupta, S. ; Pileggi, A. ; Molano, Ruth ; Ricordi, Camillo ; Shatirishvili, G. ; Loladze, G. ; Mardaleishvili, K. ; Kakabadze, M. ; Berishvili, E. / Correction of diabetes mellitus by transplanting minimal mass of syngeneic islets into vascularized small intestinal segment. In: American Journal of Transplantation. 2013 ; Vol. 13, No. 10. pp. 2550-2557.
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