Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
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Author(s)
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.
Date Issued
May 2013
Journal
Biomaterials
Publisher
Elsevier
Citation
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.
Version
Author's final manuscript
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.
MIT Department
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
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2013.04.016
