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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
Biomaterials, v 34(23), pp 5792-5801
01 Jul 2013
PMID: 23660251
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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. Published by Elsevier Ltd.
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Details
- Title
- Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
- Creators
- Tram T. Dang - Massachusetts Institute of TechnologyAnh V. Thai - Massachusetts Institute of TechnologyJoshua Cohen - Joslin Diabetes CenterJeremy E. Slosberg - Massachusetts Institute of TechnologyKarolina Siniakowicz - Joslin Diabetes CenterJoshua C. Doloff - Massachusetts Institute of TechnologyMinglin Ma - Massachusetts Institute of TechnologyJennifer Hollister-Lock - Harvard UniversityKatherine M. Tang - Massachusetts Institute of TechnologyZhen Gu - Massachusetts Institute of TechnologyHao Cheng - Massachusetts Institute of TechnologyGordon C. Weir - Joslin Diabetes CenterRobert Langer - Massachusetts Institute of TechnologyDaniel G. Anderson - Massachusetts Institute of Technology
- Publication Details
- Biomaterials, v 34(23), pp 5792-5801
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- R01DE016516 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) DE016516 / National Institute of Heath A*STAR National Science graduate fellowship from the Agency for Science, Technology and Research of Singapore; Agency for Science Technology & Research (A*STAR) Leona M and Harry B. Hemsley Charitabe Trust Juvenile Diabetes Research Foundation Tayebati Family Foundation P30CA014051 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:000320219800007
- Scopus ID
- 2-s2.0-84877797407
- Other Identifier
- 991021886378204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials