Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug
Open accessAbstract
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.
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Prior work by the authors and others showed that cellular and collagen deposition on the surface of transplanted 0.5 mm alginate microcapsules causes encapsulated islet graft death and failure to correct diabetes in STZ-treated C57BL/6 mice.
“Previously, we and others have shown that host recognition and fibrosis via cellular and collagen deposition on the surface of transplanted 0.5 mm sized alginate microcapsules results in encapsulated islet graft cell death and the failure of diabetic correction in STZ-treated C57BL/6 mice28, 37, 38.”
From Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates (2015) · cites this paper as [37]
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Self-citation
- Authors
- 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.
- Affiliations
- Massachusetts Institute of Technology (US)
- Boston Children's Hospital (US)
- Joslin Diabetes Center (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 34
- Issue
- 23
- Pages
- 5792-5801
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3901568
- OpenAlex
- W1964434647
- Cited by
- 125
- References
- 54
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 15 · 2023: 6 · 2022: 12 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 3 · 2013: 1
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (5r01de016516-10)
- National Cancer Institute (P30CA014051)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836)
- National Institute of Dental and Craniofacial Research (DE016516, R01-DE016516)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- islet encapsulation, anti-inflammatory agents, curcumin, dexamethasone, fibrotic encapsulation, alginate microcapsules, type 1 diabetes, islet transplantation, host inflammatory response, reactive oxygen species, glycemic control, chemically induced diabetes
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Anti-Inflammatory Agents, Capsules, Cathepsins, Diabetes Mellitus, Experimental, Fibrosis, Islets of Langerhans, Male, Mice, Inbred C57BL, Polyglycolic Acid, Islets of Langerhans Transplantation, Rats, Sprague-Dawley, Reactive Oxygen Species, Lactic Acid, Mice, Rats, Small Molecule Libraries
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