title: Enhanced oxygen supply improves islet viability in a new bioartificial pancreas.
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.
authors.affiliation: Beta-O2 Technologies, Kiryat Arie, Petach Tikva, Israel. u.barkai@beta-o2.com
authors.forename: Uriel
authors.initials: U
authors.lastname: Barkai
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.forename: Clark K
authors.initials: CK
authors.lastname: Colton
authors.forename: Barbara
authors.initials: B
authors.lastname: Ludwig
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Mathias D
authors.initials: MD
authors.lastname: Brendel
authors.forename: Tova
authors.initials: T
authors.lastname: Neufeld
authors.forename: Chezi
authors.initials: C
authors.lastname: Bremer
authors.forename: Assaf
authors.initials: A
authors.lastname: Leon
authors.forename: Yoav
authors.initials: Y
authors.lastname: Evron
authors.forename: Karina
authors.initials: K
authors.lastname: Yavriyants
authors.forename: Dimitri
authors.initials: D
authors.lastname: Azarov
authors.forename: Baruch
authors.initials: B
authors.lastname: Zimermann
authors.forename: Shiri
authors.initials: S
authors.lastname: Maimon
authors.forename: Noa
authors.initials: N
authors.lastname: Shabtay
authors.forename: Maria
authors.initials: M
authors.lastname: Balyura
authors.forename: Tania
authors.initials: T
authors.lastname: Rozenshtein
authors.forename: Pnina
authors.initials: P
authors.lastname: Vardi
authors.forename: Konstantin
authors.initials: K
authors.lastname: Bloch
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
authors.forename: Avi
authors.initials: A
authors.lastname: Rotem
mesh_terms: D064591:Allografts / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D020007:Implants, Experimental; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D008422:Materials Testing; D010100:Oxygen / Q000494:pharmacology*; D019397:Pancreas, Artificial; D019919:Prosthesis Implantation; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D040521:Subcutaneous Tissue / Q000187:drug effects; D014022:Tissue Survival / Q000187:drug effects*; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D010100:Oxygen