title: Islets immunoisolation using encapsulation and PEGylation, simultaneously, as a novel design.
abstract: The most important obstacle in islets transplantation for the treatment of diabetes is graft rejection by the host immune system. To solve this problem, immunosuppressive drugs should be used, but they may have several side effects. To overcome these problems, islets immunoisolation systems such as encapsulation and PEGylation have been developed. The aim of this study was to investigate the possibility of using encapsulation and PEGylation techniques simultaneously (as a novel design) for immunocamouflaging the islets of Langerhans. For this purpose, the attachment of poly-L-ornithine (PLO) onto the surface of alginate microcapsules and activated methoxy polyethylene glycol (mPEG) onto alginate-PLO microcapsules was verified by Fourier transform infrared analysis and scanning electron microscopy. Viability of the free and encapsulated islets up to the 7th day was approved by acridine orange (AO)/propidium iodide (PI). The obtained results from lymphocytes co-culturing with free and encapsulated islets (in different designs of microcapsules with one to three layers) showed that encapsulation generally reduces the immune response against the islets. However, the addition of PLO and mPEG as second and third layers to the surface of alginate microcapsules decreased interleukine-2 (IL-2) secretion against the islets more and more. Finally, two different activated mPEG, mPEG-succinimidyl carbonate (mPEG-SC) and mPEG-succinimidylvaleric acid (mPEG-SVA), used separately on the surface of microcapsules were investigated, and the results showed that IL-2 secretion was reduced 14.3% and 37.5% in comparison with the alginate-PLO microcapsules, respectively. On the other hand, mPEG-SVA was more effective than mPEG-SC, so it decreased IL-2 secretion 27.1% more than mPEG-SC.
authors.affiliation: Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, P. O. Box 14115-114, Tehran, Islamic Republic of Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Nabavimanesh
authors.affiliation: Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, P. O. Box 14115-114, Tehran, Islamic Republic of Iran. Electronic address: s.hashemi@modares.ac.ir.
authors.forename: Sameereh
authors.initials: S
authors.lastname: Hashemi-Najafabadi
authors.affiliation: Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, P. O. Box 14115-114, Tehran, Islamic Republic of Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Vasheghani-Farahani
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002214:Capsules; D018920:Coculture Techniques; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D007376:Interleukin-2; D010455:Peptides; C099846:succinimidyl carbonate poly(ethylene glycol) monomethyl ether; C008973:polyornithine; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; C028210:monomethoxypolyethylene glycol
keywords: Encapsulation; Interleukine-2; Islets of Langerhans; Methoxy polyethylene glycol; PEGylation; Poly-l-ornithine