2011 - IPITA - Prague


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Parallel session 12 – Open oral presentations Topic: Immunoisolation and assessment of the islet graft

12.5 - Islet sparing potential of a subcutaneous Cell Pouch™ for allogeneic islet transplantation

Presenter: Delfina M., Andrew R., Mazzuca, Pepper, London, Canada
Authors: Delfina M. Mazzuca , Andrew R. Pepper, Mandy MacGillivary, Anthony Bruni, Vishaal Gupta, D.J.G White, P.M. Toleikis


Islet sparing potential of a subcutaneous Cell Pouch™ for allogeneic islet transplantation

Delfina M. Mazzuca 1, Andrew R. Pepper1, Mandy MacGillivary1, Anthony Bruni1, Vishaal Gupta1, D.J.G White2, P.M. Toleikis1
1 Sernova Corp, London, Canada; 2 University of Western Ontario, London, Canada

Objective: Pancreatic islet transplantation through portal infusion has shown some promise as a therapy for restoring carbohydrate control to the insulin dependent diabetic patient; however, this procedure may require multiple pancreata. The safety and efficacy of a prevascularized subcutaneous proprietary Cell Pouch™ has been recently demonstrated in a stringent large animal autograft study. The current study examines the potential islet sparing capacity of the Cell Pouch™ in a porcine islet-allograft model.

Methods: Approximately one year old female miniature Gottingen pigs were implanted with two subcutaneous Cell Pouches™, six to eight weeks prior to receiving an islet allograft. Donor islets were procured and isolated from >2 year old retired breeder Yorkshire-Landrace pigs. One to three weeks prior to transplant, diabetes was chemically induced by dosing animals intravenously with 150 mg/kg of streptozotocin. To ensure a stringent hyperglycemic state, diabetic intravenous glucose tolerance tests (IVGTTs) were performed prior to islet transplantation. Recipient mini-pigs were transplanted with allogeneic islets ranging from 2,500-10,000IEQ/kg into the prevascularized subcutaneous Cell Pouch™. An immunosuppression regimen of Cyclosporine and Sirolimus was employed to prevent graft rejection within recipients. Graft function was monitored using standard tests.

Results: Preliminary data indicate that a marginal islet mass is efficacious in its ability to restore glucose control post-transplant into the Cell Pouch™. This has been demonstrated by a reduction in daily blood glucose levels and insulin requirements, improved IVGTT glucose tolerance test and insulin secretion post-transplant. Robust vascular networks have been observed within the islet graft upon Cell Pouch™ explantation.

Conclusions: The islet sparing properties of the Cell Pouch™, in this large animal allograft diabetes model support its evaluation for clinical islet transplantation.


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