dc.contributor.author | Evron, Yoav | |
dc.contributor.author | Colton, Clark K. | |
dc.contributor.author | Ludwig, Barbara | |
dc.contributor.author | Weir, Gordon C. | |
dc.contributor.author | Zimermann, Baruch | |
dc.contributor.author | Maimon, Shiri | |
dc.contributor.author | Neufeld, Tova | |
dc.contributor.author | Shalev, Nurit | |
dc.contributor.author | Goldman, Tali | |
dc.contributor.author | Leon, Assaf | |
dc.contributor.author | Yavriyants, Karina | |
dc.contributor.author | Shabtay, Noa | |
dc.contributor.author | Rozenshtein, Tania | |
dc.contributor.author | Azarov, Dimitri | |
dc.contributor.author | DiIenno, Amanda R. | |
dc.contributor.author | Steffen, Anja | |
dc.contributor.author | de Vos, Paul | |
dc.contributor.author | Bornstein, Stefan R. | |
dc.contributor.author | Barkai, Uriel | |
dc.contributor.author | Rotem, Avi | |
dc.contributor.author | Colton, Clark K | |
dc.contributor.author | DiIenno, Amanda Rose | |
dc.date.accessioned | 2018-10-22T18:49:14Z | |
dc.date.available | 2018-10-22T18:49:14Z | |
dc.date.issued | 2018-04 | |
dc.date.submitted | 2017-09 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/118745 | |
dc.description.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. | en_US |
dc.description.sponsorship | Israel. Ministry of Science | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/S41598-018-23862-W | en_US |
dc.rights | Creative Commons Attribution 4.0 International License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | Nature | en_US |
dc.title | Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply | en_US |
dc.type | Article | en_US |
dc.identifier.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. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.mitauthor | Colton, Clark K | |
dc.contributor.mitauthor | DiIenno, Amanda Rose | |
dc.relation.journal | Scientific Reports | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-10-11T16:28:11Z | |
dspace.orderedauthors | 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 | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8777-9632 | |
dc.identifier.orcid | https://orcid.org/0000-0002-4259-480X | |
mit.license | PUBLISHER_CC | en_US |