Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply
Author(s)
Evron, Yoav; Colton, Clark K.; Ludwig, Barbara; Weir, Gordon C.; Zimermann, Baruch; Maimon, Shiri; Neufeld, Tova; Shalev, Nurit; Goldman, Tali; Leon, Assaf; Yavriyants, Karina; Shabtay, Noa; Rozenshtein, Tania; Azarov, Dimitri; DiIenno, Amanda R.; Steffen, Anja; de Vos, Paul; Bornstein, Stefan R.; Barkai, Uriel; Rotem, Avi; Colton, Clark K; DiIenno, Amanda Rose; ... Show more Show less
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Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO[subscript 2]. Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO[subscript 2] to a supraphysiological level that maintains all islets viable and functional. These levels were determined from measurements of pO[subscript 2] profiles in islet-alginate slabs. Encapsulated islets implanted with surface density as high as 4,800 islet equivalents/cm[superscrip 3] in diabetic rats maintained normoglycemia for more than 7 months and provided near-normal intravenous glucose tolerance tests. Nearly 90% of the original viable tissue was recovered after device explantation. Damaged islets failed after progressively shorter times. The required values of gas chamber p[subscript O] were predictable from a mathematical model of oxygen consumption and diffusion in the device. These results demonstrate feasibility of developing retrievable macroencapsulated devices small enough for clinical use and provide a firm basis for design of devices for testing in large animals and humans.
Date issued
2018-04Department
Massachusetts Institute of Technology. Department of Chemical EngineeringJournal
Scientific Reports
Publisher
Springer Nature
Citation
Evron, Yoav, et al. “Long-Term Viability and Function of Transplanted Islets Macroencapsulated at High Density Are Achieved by Enhanced Oxygen Supply.” Scientific Reports, vol. 8, no. 1, Dec. 2018.
Version: Final published version
ISSN
2045-2322