Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function
Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO_2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO_2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes.
Additional Information© 2016 Elsevier. Received 23 December 2015. Accepted 18 January 2016. Available online 20 January 2016. H.K. designed the study, collected data, and wrote the manuscript. D.K., L.M., A.B. and D.M. collected data. J.R., K.O, K.F., Y.T., F.K. and Y.M. reviewed and edited the manuscript. This work was supported by a grant from the Nora Eccles Treadwell Foundation (30.6990.973667). Human islets were provided by the Integrated Islet Distribution Program (IIDP). We acknowledge the Manufacturing Team led by Dr. Ismail Al-Abdullah at the Southern California Islet Cell Resources Center, Beckman Research Institute of City of Hope for preparation of human islets. We also thank Dr. Chris Gandhi for critical reading and editing of the manuscript.
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