Enhanced function of immuno-isolated islets in diabetes therapy byco-encapsulation with an anti-inflammatory drug

Tram T. Dang, Anh V. Thai, Joshua Cohen, Jeremy E. Slosberg, Karolina Siniakowicz, Joshua C. Doloff, Minglin Ma, Jennifer Hollister-Lock, Katherine M. Tang, Zhen Gu, Hao Cheng, Gordon C. Weir, Robert Langer, Daniel G. Anderson

Research output: Contribution to journalArticle

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. Invivo 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.

Original languageEnglish (US)
Pages (from-to)5792-5801
Number of pages10
JournalBiomaterials
Volume34
Issue number23
DOIs
StatePublished - Jul 1 2013

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Keywords

  • Anti-inflammatory drugs
  • Curcumin
  • Diabetes
  • Encapsulated islets
  • Fibrotic overgrowth
  • Host response

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Dang, T. T., Thai, A. V., Cohen, J., Slosberg, J. E., Siniakowicz, K., Doloff, J. C., Ma, M., Hollister-Lock, J., Tang, K. M., Gu, Z., Cheng, H., Weir, G. C., Langer, R., & Anderson, D. G. (2013). Enhanced function of immuno-isolated islets in diabetes therapy byco-encapsulation with an anti-inflammatory drug. Biomaterials, 34(23), 5792-5801. https://doi.org/10.1016/j.biomaterials.2013.04.016