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Published on: November 5, 2016
Maintenance of aerobic metabolism increases immunoisolated islet survival
John I Stagner1, Ratnam S Seelan, Ranga N Parthasarathy
1Robley Rex Department of Veterans Affairs Medical Center, Louisville, KY, USA. john.stagner@va.gov
The progress of immunoisolation as a treatment for diabetes has been hampered by the diminished long term viability of islets within the immunoisolation device. Chronic hypoxia is greatly responsible for islet cell death within an immunoisolation device and remains an obstacle to the success of this form of islet transplantation. In order to address this problem, isolated rat islets were transfected with a plasmid encoding cytoglobin, an intracellular oxygen binding protein. Untreated or transfected islets were placed in polyacrylonitrile-polyvinychloride hollow fiber and implanted beneath the hepatic capsule in streptozotocin-diabetic rats. Fasting blood glucose was used as an indicator of islet survival and function. Rats receiving fibers containing transfected islets remained normoglycemic through the 60 day trial. Untreated islets failed within two weeks after implantation resulting in elevated blood glucose in the recipient. The fibers were recovered and tested for insulin content. Cytoglobin promoted islet cell survival and insulin synthesis and secretion. The induction of cytoglobin in islets may reduce cell loss from chronic hypoxia and may be a useful method to improve the feasibility of immunoisolation as an islet transplantation modality.
The progress of immunoisolation as a treatment for diabetes has been hampered by the diminished long term viability of islets within the immunoisolation device. Chronic hypoxia is greatly responsible for islet cell death within an immunoisolation device and remains an obstacle to the success of this form of islet transplantation. In order to address this problem, isolated rat islets were transfected with a plasmid encoding cytoglobin, an intracellular oxygen binding protein. Untreated or transfected islets were placed in polyacrylonitrile-polyvinychloride hollow fiber and implanted beneath the hepatic capsule in streptozotocin-diabetic rats. Fasting blood glucose was used as an indicator of islet survival and function. Rats receiving fibers containing transfected islets remained normoglycemic through the 60 day trial. Untreated islets failed within two weeks after implantation resulting in elevated blood glucose in the recipient. The fibers were recovered and tested for insulin content. Cytoglobin promoted islet cell survival and insulin synthesis and secretion. The induction of cytoglobin in islets may reduce cell loss from chronic hypoxia and may be a useful method to improve the feasibility of immunoisolation as an islet transplantation modality.
