title: Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug.
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.
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors: Tram T
authors: TT
authors: Dang
authors: Anh V
authors: AV
authors: Thai
authors: Joshua
authors: J
authors: Cohen
authors: Jeremy E
authors: JE
authors: Slosberg
authors: Karolina
authors: K
authors: Siniakowicz
authors: Joshua C
authors: JC
authors: Doloff
authors: Minglin
authors: M
authors: Ma
authors: Jennifer
authors: J
authors: Hollister-Lock
authors: Katherine M
authors: KM
authors: Tang
authors: Zhen
authors: Z
authors: Gu
authors: Hao
authors: H
authors: Cheng
authors: Gordon C
authors: GC
authors: Weir
authors: Robert
authors: R
authors: Langer
authors: Daniel G
authors: DG
authors: Anderson
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002214:Capsules / Q000737:chemistry*; D002403:Cathepsins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000628:therapy*; D005355:Fibrosis; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D016381:Islets of Langerhans Transplantation; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D002214:Capsules; D017382:Reactive Oxygen Species; D054852:Small Molecule Libraries; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002403:Cathepsins
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