Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device

Antonello Pileggi, Ruth Molano, Camillo Ricordi, Elsie Zahr, Jill Collins, Rafael Valdes, Luca A Inverardi

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

BACKGROUND.: Transplantation of pancreatic islets for the treatment of type 1 diabetes allows for physiologic glycemic control and insulin-independence when sufficient islets are implanted via the portal vein into the liver. Intrahepatic islet implantation requires specific infrastructure and expertise, and risks inherent to the procedure include bleeding, thrombosis, and elevation of portal pressure. Additionally, the relatively higher drug metabolite concentrations in the liver may contribute to the delayed loss of graft function of recent clinical trials. Identification of alternative implantation sites using biocompatible devices may be of assistance improving graft outcome. A desirable bioartificial pancreas should be easy to implant, biopsy, and retrieve, while allowing for sustained graft function. The subcutaneous (SC) site may require a minimally invasive procedure performed under local anesthesia, but its use has been hampered so far by lack of early vascularization, induction of local inflammation, and mechanical stress on the graft. METHODS.: Chemically diabetic rats received syngeneic islets into the liver or SC into a novel biocompatible device consisting of a cylindrical stainless-steel mesh. The device was implanted 40 days prior to islet transplantation to allow embedding by connective tissue and neovascularization. Reversal of diabetes and glycemic control was monitored after islet transplantation. RESULTS.: Syngeneic islets transplanted into a SC, neovascularized device restored euglycemia and sustained function long-term. Removal of graft-bearing devices resulted in hyperglycemia. Explanted grafts showed preserved islets and intense vascular networks. CONCLUSIONS.: Ease of implantation, biocompatibility, and ability to maintain long-term graft function support the potential of our implantable device for cellular-based reparative therapies.

Original languageEnglish
Pages (from-to)1318-1324
Number of pages7
JournalTransplantation
Volume81
Issue number9
DOIs
StatePublished - May 1 2006

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Islets of Langerhans Transplantation
Transplants
Equipment and Supplies
Liver
Delayed Graft Function
Portal Pressure
Mechanical Stress
Stainless Steel
Local Anesthesia
Portal Vein
Type 1 Diabetes Mellitus
Hyperglycemia
Connective Tissue
Blood Vessels
Pancreas
Thrombosis
Clinical Trials
Insulin
Hemorrhage
Inflammation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device. / Pileggi, Antonello; Molano, Ruth; Ricordi, Camillo; Zahr, Elsie; Collins, Jill; Valdes, Rafael; Inverardi, Luca A.

In: Transplantation, Vol. 81, No. 9, 01.05.2006, p. 1318-1324.

Research output: Contribution to journalArticle

Pileggi, Antonello ; Molano, Ruth ; Ricordi, Camillo ; Zahr, Elsie ; Collins, Jill ; Valdes, Rafael ; Inverardi, Luca A. / Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device. In: Transplantation. 2006 ; Vol. 81, No. 9. pp. 1318-1324.
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