title: Oxygen supply by photosynthesis to an implantable islet cell device.
abstract: Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically-generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660 nm, intensity of 8 μE/m(2)/s). Islet cells immobilized in an alginate slab (500-1,000 islet equivalents/cm(2)) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4 μm) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality.
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Evron
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Zimermann
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Ludwig
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Barkai
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Colton
authors.affiliation: Section of islet Transplantation and Cell Biology, Joslin Diabetes Center, Research Division, One Joslin Place, Boston, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Weir
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Arieli
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Maimon
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Shalev
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Yavriyants
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Goldman
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Gendler
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Eizen
authors.affiliation: Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Beilinson Campus, Petah Tikva, Israel.
authors.forename: P
authors.initials: P
authors.lastname: Vardi
authors.affiliation: Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Beilinson Campus, Petah Tikva, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Bloch
authors.affiliation: University Hospital Carl Gustav Carus, Department of Medicine III, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Barthel
authors.affiliation: University Hospital Carl Gustav Carus, Department of Medicine III, Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Beta-O2 Technologies, Rosh Ha'ain, Afek Park, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Rotem
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010788:Photosynthesis; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D046940:Synechococcus / Q000378:metabolism
chemical_list: D010100:Oxygen