Open Access

Enhanced Oxygen Supply Improves Islet Viability in a New Bioartificial Pancreas

Authors: Barkai, Uriel; Weir, Gordon C.; Colton, Clark K.; Ludwig, Barbara; Bornstein, Stefan R.; Brendel, Mathias D.; Neufeld, Tova; Bremer, Chezi; Leon, Assaf; Evron, Yoav; Yavriyants, Karina; Azarov, Dimitri; Zimermann, Baruch; Maimon, Shiri; Shabtay, Noa; Balyura, Maria; Rozenshtein, Tania; Vardi, Pnina; Bloch, Konstantin; de Vos, Paul; Rotem, Avi

Source: Cell Transplantation, Volume 22, Number 8, August 2013 , pp. 1463-1476(14)

Publisher: Cognizant Communication Corporation

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Abstract:

The current epidemic of diabetes with its overwhelming burden on our healthcare system requires better therapeutic strategies. Here we present a promising novel approach for a curative strategy that may be accessible for all insulin-dependent diabetes patients. We designed a subcutaneous implantable bioartificial pancreas (BAP)—the “β-Air”—that is able to overcome critical challenges in current clinical islet transplantation protocols: adequate oxygen supply to the graft and protection of donor islets against the host immune system. The system consists of islets of Langerhans immobilized in an alginate hydrogel, a gas chamber, a gas permeable membrane, an external membrane, and a mechanical support. The minimally invasive implantable device, refueled with oxygen via subdermally implanted access ports, completely normalized diabetic indicators of glycemic control (blood glucose intravenous glucose tolerance test and HbA1c) in streptozotocin-induced diabetic rats for periods up to 6 months. The functionality of the device was dependent on oxygen supply to the device as the grafts failed when oxygen supply was ceased. In addition, we showed that the device is immuno-protective as it allowed for survival of not only isografts but also of allografts. Histological examination of the explanted devices demonstrated morphologically and functionally intact islets; the surrounding tissue was without signs of inflammation and showed visual evidence of vasculature at the site of implantation. Further increase in islets loading density will justify the translation of the system to clinical trials, opening up the potential for a novel approach in diabetes therapy.

Keywords: Bioartificial pancreas (BAP); Diabetes; Immune barrier; Implantation; Islets; Oxygen

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368912X657341

Publication date: August 9, 2013

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

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