Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device

Y. Evron; B. Zimermann; B. Ludwig; U. Barkai; C. K. Colton; G. C. Weir; B. Arieli; S. Maimon; N. Shalev; K. Yavriyants; T. Goldman; Z. Gendler; L. Eizen; P. Vardi; K. Bloch; A. Barthel; S. R. Bornstein; A. Rotem

doi:10.1055/s-0034-1394375

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2015; 47(01): 24-30
DOI: 10.1055/s-0034-1394375

Endocrine Care

Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device

Y. Evron

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

B. Zimermann

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

B. Ludwig

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

²University Hospital Carl Gustav Carus, Department of Medicine III, Dresden, Germany

,

U. Barkai

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

C. K. Colton

³Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA

,

G. C. Weir

⁴Section of islet Transplantation and Cell Biology, Joslin Diabetes Center, Research Division, One Joslin Place, Boston, USA

,

B. Arieli

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

S. Maimon

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

N. Shalev

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

K. Yavriyants

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

T. Goldman

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

Z. Gendler

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

L. Eizen

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

,

P. Vardi

⁵Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Beilinson Campus, Petah Tikva, Israel

,

K. Bloch

⁵Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Beilinson Campus, Petah Tikva, Israel

,

A. Barthel

²University Hospital Carl Gustav Carus, Department of Medicine III, Dresden, Germany

⁶Endokrinologikum Ruhr, Bochum, Germany

,

S. R. Bornstein

²University Hospital Carl Gustav Carus, Department of Medicine III, Dresden, Germany

,

A. Rotem

¹Beta-O2 Technologies, Rosh Ha’ain, Afek Park, Israel

› Author Affiliations

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/m²/s). Islet cells immobilized in an alginate slab (500–1 000 islet equivalents/cm²) 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.

Key words

type 1 diabetes - bioartificial pancreas - cyanobacteria

Full Text

References

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