Enhanced Oxygen Supply Improves Islet Viability in a New Bioartificial Pancreas

Cell Transplantation

Article

Maria Balyura¹  Assaf Leon¹  Noa Shabtay¹  Karina Yavriyants¹  Avi Rotem¹  Tova Neufeld¹  Chezi Bremer¹  Dimitri Azarov¹  Shiri Maimon¹  Uriel Barkai¹  Tania Rozenshtein¹  Baruch Zimermann¹  Yoav Evron¹  Clark K. Colton²  Pnina Vardi³  Paul De Vos⁴  Konstantin Bloch⁵  Gordon C. Weir⁶  Mathias D. Brendel⁷  Stefan R. Bornstein⁷  Barbara Ludwig⁷ 

[1] Beta-O Technologies, Kiryat Arie, Petach Tikva, Israel;Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;Department of Diabetes, Lin Medical Center, Clalit Health Services, Haifa, Israel;Department of Pathology and Laboratory Medicine, Section of Immunoendocrinology, University Medical Center Groningen, Groningen, The Netherlands;Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Beilinson Campus, Petah Tikva, Israel;Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Research Division, Boston, MA, USA;University Hospital Carl Gustav Carus, Department of Medicine III, Dresden, Germany;

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

DOI  :  10.3727/096368912X657341

 received in 2012-01-18, accepted in 2012-07-18,  发布年份 2013

来源: Sage Journals

【 摘 要 】

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 immunoprotective 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.

【 授权许可】

Unknown   
© 2013 Cognizant Comm. Corp.

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