TY - JOUR
T1 - Oxygen supply by photosynthesis to an implantable islet cell device
AU - Evron, Y.
AU - Zimermann, B.
AU - Ludwig, B.
AU - Barkai, U.
AU - Colton, C. K.
AU - Weir, G. C.
AU - Arieli, B.
AU - Maimon, S.
AU - Shalev, N.
AU - Yavriyants, K.
AU - Goldman, T.
AU - Gendler, Z.
AU - Eizen, L.
AU - Vardi, P.
AU - Bloch, K.
AU - Barthel, A.
AU - Bornstein, S. R.
AU - Rotem, A.
N1 - Publisher Copyright:
© © Georg Thieme Verlag KG Stuttgart, New York.
PY - 2015/1
Y1 - 2015/1
N2 - 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.
AB - 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.
KW - bioartificial pancreas
KW - cyanobacteria
KW - type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84920736191&partnerID=8YFLogxK
U2 - 10.1055/s-0034-1394375
DO - 10.1055/s-0034-1394375
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C2 - 25365509
AN - SCOPUS:84920736191
SN - 0018-5043
VL - 47
SP - 24
EP - 30
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
IS - 1
ER -
