A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo
The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating device...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2024
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| Online Access: | https://hdl.handle.net/1721.1/156886 |
| _version_ | 1824458345250029568 |
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| author | Krishnan, Siddharth R Liu, Claudia Bochenek, Matthew A Bose, Suman Khatib, Nima Walters, Ben O’Keeffe, Laura Facklam, Amanda Langer, Robert Anderson, Daniel G |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Krishnan, Siddharth R Liu, Claudia Bochenek, Matthew A Bose, Suman Khatib, Nima Walters, Ben O’Keeffe, Laura Facklam, Amanda Langer, Robert Anderson, Daniel G |
| author_sort | Krishnan, Siddharth R |
| collection | MIT |
| description | The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals. |
| first_indexed | 2024-09-23T15:16:56Z |
| format | Article |
| id | mit-1721.1/156886 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:24:25Z |
| publishDate | 2024 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1568862025-01-02T04:43:37Z A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo Krishnan, Siddharth R Liu, Claudia Bochenek, Matthew A Bose, Suman Khatib, Nima Walters, Ben O’Keeffe, Laura Facklam, Amanda Langer, Robert Anderson, Daniel G Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Institute for Medical Engineering & Science The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals. 2024-09-17T18:03:00Z 2024-09-17T18:03:00Z 2023-10-03 2024-09-17T17:25:25Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/156886 Krishnan, Siddharth R, Liu, Claudia, Bochenek, Matthew A, Bose, Suman, Khatib, Nima et al. 2023. "A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo." Proceedings of the National Academy of Sciences, 120 (40). en 10.1073/pnas.2311707120 Proceedings of the National Academy of Sciences Creative Commons Attribution-NonCommercial-NoDerivs License https://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences |
| spellingShingle | Krishnan, Siddharth R Liu, Claudia Bochenek, Matthew A Bose, Suman Khatib, Nima Walters, Ben O’Keeffe, Laura Facklam, Amanda Langer, Robert Anderson, Daniel G A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| title | A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| title_full | A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| title_fullStr | A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| title_full_unstemmed | A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| title_short | A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| title_sort | wireless battery free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo |
| url | https://hdl.handle.net/1721.1/156886 |
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