Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated an...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101126 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0002-4323-3264 https://orcid.org/0000-0003-4255-0492 |
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| author | Dang, Tram T. Thai, Anh V. Slosberg, Jeremy E. Siniakowicz, Karolina Ma, Minglin Hollister-Lock, Jennifer Tang, Katherine M. Gu, Zhen Cheng, Hao Weir, Gordon C. Anderson, Daniel Griffith Tang, Katherine Langer, Robert S Cohen, Joshua, 1951- Doloff, Joshua C |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Dang, Tram T. Thai, Anh V. Slosberg, Jeremy E. Siniakowicz, Karolina Ma, Minglin Hollister-Lock, Jennifer Tang, Katherine M. Gu, Zhen Cheng, Hao Weir, Gordon C. Anderson, Daniel Griffith Tang, Katherine Langer, Robert S Cohen, Joshua, 1951- Doloff, Joshua C |
| author_sort | Dang, Tram T. |
| collection | MIT |
| description | Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes. |
| first_indexed | 2024-09-23T14:24:11Z |
| format | Article |
| id | mit-1721.1/101126 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:24:11Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1011262022-10-01T21:09:19Z Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug Dang, Tram T. Thai, Anh V. Slosberg, Jeremy E. Siniakowicz, Karolina Ma, Minglin Hollister-Lock, Jennifer Tang, Katherine M. Gu, Zhen Cheng, Hao Weir, Gordon C. Anderson, Daniel Griffith Tang, Katherine Langer, Robert S Cohen, Joshua, 1951- Doloff, Joshua C Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Dang, Tram T. Thai, Anh V. Slosberg, Jeremy E. Doloff, Joshua C. Ma, Minglin Tang, Katherine Gu, Zhen Cheng, Hao Langer, Robert Anderson, Daniel Griffith Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes. Juvenile Diabetes Research Foundation International Leona M. and Harry B. Helmsley Charitable Trust National Institutes of Health (U.S.) (Grant DE016516) Singapore. Agency for Science, Technology and Research (National Science Graduate Fellowship) Tayebati Family Foundation 2016-02-09T14:35:06Z 2016-02-09T14:35:06Z 2013-05 2013-01 Article http://purl.org/eprint/type/JournalArticle 01429612 1878-5905 http://hdl.handle.net/1721.1/101126 Dang, Tram T., Anh V. Thai, Joshua Cohen, Jeremy E. Slosberg, Karolina Siniakowicz, Joshua C. Doloff, Minglin Ma, et al. “Enhanced Function of Immuno-Isolated Islets in Diabetes Therapy by Co-Encapsulation with an Anti-Inflammatory Drug.” Biomaterials 34, no. 23 (July 2013): 5792–5801. https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0002-4323-3264 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1016/j.biomaterials.2013.04.016 Biomaterials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Dang, Tram T. Thai, Anh V. Slosberg, Jeremy E. Siniakowicz, Karolina Ma, Minglin Hollister-Lock, Jennifer Tang, Katherine M. Gu, Zhen Cheng, Hao Weir, Gordon C. Anderson, Daniel Griffith Tang, Katherine Langer, Robert S Cohen, Joshua, 1951- Doloff, Joshua C Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug |
| title | Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug |
| title_full | Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug |
| title_fullStr | Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug |
| title_full_unstemmed | Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug |
| title_short | Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug |
| title_sort | enhanced function of immuno isolated islets in diabetes therapy by co encapsulation with an anti inflammatory drug |
| url | http://hdl.handle.net/1721.1/101126 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0002-4323-3264 https://orcid.org/0000-0003-4255-0492 |
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