Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply
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 replenishab...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Springer Nature
2018
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| Online Access: | http://hdl.handle.net/1721.1/118745 https://orcid.org/0000-0001-8777-9632 https://orcid.org/0000-0002-4259-480X |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering 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 |
| author_sort | Evron, Yoav |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:14:43Z |
| format | Article |
| id | mit-1721.1/118745 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:14:43Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1187452022-09-28T19:27:46Z Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply 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 Massachusetts Institute of Technology. Department of Chemical Engineering Colton, Clark K DiIenno, Amanda Rose 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. Israel. Ministry of Science 2018-10-22T18:49:14Z 2018-10-22T18:49:14Z 2018-04 2017-09 2018-10-11T16:28:11Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/118745 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. https://orcid.org/0000-0001-8777-9632 https://orcid.org/0000-0002-4259-480X http://dx.doi.org/10.1038/S41598-018-23862-W Scientific Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Nature |
| spellingShingle | 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 Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| title | Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| title_full | Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| title_fullStr | Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| title_full_unstemmed | Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| title_short | Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| title_sort | long term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply |
| url | http://hdl.handle.net/1721.1/118745 https://orcid.org/0000-0001-8777-9632 https://orcid.org/0000-0002-4259-480X |
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