Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply
Name
s41598-018-23862-w.pdf
Size
1.77 MB
Format
Adobe PDF
Checksum (MD5)
9c0bf044f297ba5da44e8c94f168476b
Author(s)
Evron, Yoav
Colton, Clark K.
Ludwig, Barbara
Weir, Gordon C.
Zimermann, Baruch
Maimon, Shiri
Neufeld, Tova
Shalev, Nurit
Goldman, Tali
Leon, Assaf
Date Issued
April 2018
Journal
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
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41598-018-23862-W
