P-252

Implantation of 'betaAir' devices containing donor islets at high density result in restoration of glycemic control in diabetic rats

Y. Evron, U. Barkai, T. Neufeld, C. Bremer, A. Leon, D. Azarov, I. Sarasenko, K. Yavriyants, S. Maimon, M. Roizblatt, T. Goldman, N. Shalev, N. Shabtay, I. Maschenko, F. Yankelevich, T. Rozenshtein, E. Ron, T. Shimon, D. Lorber, A. Rotem
Beta-O2 Technologies, Petach Tikva, Israel

Enzymatic isolation of pancreatic islets totally disrupts their blood supply. Consequently, transplanted islets solely rely on diffusion mechanism for nutrients uptake and for insulin secretion. Encapsulation of isolated islets in hydrogels only aggravates this situation and oxygen - highly consumed by islets - is quickly becoming a limiting factor for their normal functioning. To overcome this limitation, Beta O2 Technologies developed the bAir^® bio-artificial pancreas (BAP). The device is implanted under the skin equipped with donor islets of Langerhans immobilized in a flat sheet hydrogel. It is protected from the host immune system by a three layer immune barrier consisting of hydrophilized Teflon membrane and two types of alginate. Oxygen is supplied to the islets from an integrated gas chamber via a gas permeable membrane following daily refueling of the gas chamber. The device, containing 2,500 IEQ at a density of 1,000 IEQ/cm^2, was successfully tested on isogeneic and allogenic diabetic rats for periods of up to 6 months. In order to reduce the size of the device, the density of the islets must be increased which may ask for increased oxygen supply. To test this assumption, islets, at different densities, were integrated in 'bAir^®' devices, implanted in diabetic rats and supplied with various oxygen concentrations. Daily refueling with gas mixture containing 40% oxygen was sufficient to support functional islets and good glycemic control at a planar density of 2,400 IEQ/cm^2. However, in order to be able to support glycemic control at density of 4,800 IEQ/cm^2, the infused oxygen concentration was increased to 75%. Reverse of diabetes markers was demonstrated. These results revealed the ability of the bAir^® to cure diabetes in rats implanted with donor islets at a very high density. This ability translates into a small BAP device adequate for implantation.

P-252

Implantation of 'betaAir' devices containing donor islets at high density result in restoration of glycemic control in diabetic rats

Y. Evron, U. Barkai, T. Neufeld, C. Bremer, A. Leon, D. Azarov, I. Sarasenko, K. Yavriyants, S. Maimon, M. Roizblatt, T. Goldman, N. Shalev, N. Shabtay, I. Maschenko, F. Yankelevich, T. Rozenshtein, E. Ron, T. Shimon, D. Lorber, A. Rotem
Beta-O2 Technologies, Petach Tikva, Israel

Enzymatic isolation of pancreatic islets totally disrupts their blood supply. Consequently, transplanted islets solely rely on diffusion mechanism for nutrients uptake and for insulin secretion. Encapsulation of isolated islets in hydrogels only aggravates this situation and oxygen - highly consumed by islets - is quickly becoming a limiting factor for their normal functioning. To overcome this limitation, Beta O2 Technologies developed the bAir^® bio-artificial pancreas (BAP). The device is implanted under the skin equipped with donor islets of Langerhans immobilized in a flat sheet hydrogel. It is protected from the host immune system by a three layer immune barrier consisting of hydrophilized Teflon membrane and two types of alginate. Oxygen is supplied to the islets from an integrated gas chamber via a gas permeable membrane following daily refueling of the gas chamber. The device, containing 2,500 IEQ at a density of 1,000 IEQ/cm^2, was successfully tested on isogeneic and allogenic diabetic rats for periods of up to 6 months. In order to reduce the size of the device, the density of the islets must be increased which may ask for increased oxygen supply. To test this assumption, islets, at different densities, were integrated in 'bAir^®' devices, implanted in diabetic rats and supplied with various oxygen concentrations. Daily refueling with gas mixture containing 40% oxygen was sufficient to support functional islets and good glycemic control at a planar density of 2,400 IEQ/cm^2. However, in order to be able to support glycemic control at density of 4,800 IEQ/cm^2, the infused oxygen concentration was increased to 75%. Reverse of diabetes markers was demonstrated. These results revealed the ability of the bAir^® to cure diabetes in rats implanted with donor islets at a very high density. This ability translates into a small BAP device adequate for implantation.