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Beta-Air®, a subcutaneous implantable, oxygen supported, bio-artificial pancreas, restores glycemic control in xenogeneic diabetic mini-pig model

Uriel Barkai, Yoav Evron, Karina Yavriants, Dimitri Azarov, Baruch Zimermann, Maria Balyura, Ehud Ron, Zvi Shimon, Nurit Shalev, Shiri Maimon, Tania Rozenshtein, Chezi Bremer, Dana Lorber, Tova Neufeld, Avi Rotem

Beta-O2 Technologies, CSO, Petach Tikva, Israel

β-Air^® is a subcutaneous implantable bio-artificial pancreas (BAP). The mechanical platform of the device is designed to overcome two critical challenges to the development of an implantable BAP: adequate oxygen supply and protection of donor islets against the host immune system. The β-Air BAP consists of Islets of Langerhans (IOL) immobilized in alginate hydrogel (Islets), gas tank (O₂ Tank), gas permeable membrane, external Teflon^® membrane, and mechanical supports (external and internal grids) (Figure 1). Previously, we demonstrated that a rat-type β-Air BAP refueled once a day with an oxygen-enriched gas blend was able to restore glycemic control in isogeneic and allogeneic diabetic rat recipients for a period of 90-180 days. We developed a larger version of this device, which is able to support up to 130,000 islet equivalents. This version includes a compartmentalized air tank and an alginate-embedded Teflon^® membrane. Sinclair mini-pigs were rendered diabetic by three consecutive intravenous infusions of Zanosar™ and diabetic markers were allowed to develop for three to four weeks. Subsequently, a β-Air BAP device consisting of rat islets was implanted under the skin of 6 recipients. The device was refueled daily with a gas blend including 95% oxygen. Non-fasting blood glucose levels and pharmacokinetic profiles following glucose load (intravenous glucose tolerance test) were normalized for a period of 30-60 days. Molecular analyses (PCR and antibody titer) showed no infiltration of host cells into the device lumen and a negligible porcine anti-rat antibody titer. In one implanted minipig, serum rat C-peptide, averaging 300 pg/ml, was evident for a period of 60 days. Our results demonstrate the ability of the b-Air BAP device containing rat islets to treat diabetes in mini-pigs.