A new strategy toward improving immunoprotection in cell therapy for diabetes mellitus: long-functioning PEGylated islets in vivo.
Surface modification of islets using poly(ethylene glycol) (PEG) has been studied toward preventing immune responses of host for successful islet transplantation. In this study, we assessed the functionality of PEGylated islets and immune responses of host, as well as the synergistic effects of using PEGylation simultaneously with cyclosporine A (CsA) to prevent immune reactions. The average period of time for which PEGylated islets functioned normally following islets transplantation was 14 days, whereas it was only 5 days for unmodified islets. Host's immune cells did not eliminate the PEGylated islets but were observed to gather around the islets. On the other hand, unmodified islets were completely eliminated. When a low dose of CsA (3 mg/kg/day) was intravenously administered at the same time, the PEGylated islets showed stable activity and survived for 100 days before, that is, the PEGylated islets secreted insulin and were preserved from the immune cells. However, unmodified islets survived for 14 days on the average, even when CsA was administered. Consequently, it can be suggested that the PEGylation of islet surfaces can be an effective approach toward reducing the immunogenecity of islets, thus improving the functionality and survival time of transplanted islets, especially when CsA was simultaneously administered.
Lee
Dong Yun
DY
College of Pharmacy, Seoul National University, Seoul, South Korea.
Park
Sang Jin
SJ
Nam
Jong Hee
JH
Byun
Youngro
Y
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods* / Q000473:pathology; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods
D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; D016572:Cyclosporine