title: The effects of 8-arm-PEG-catechol/heparin shielding system and immunosuppressive drug, FK506 on the survival of intraportally allotransplanted islets.
abstract: This study proposed a double-layer shielding method of using 8-arm-PEG-catechol (PEG(8)) and N-hydroxysuccinimidyl-linked unfractionated heparin (UFH-NHS) for the prevention of instant blood-mediated inflammatory reaction (IBMIR) and immune reactions against transplanted pancreatic islets. The surface of islet was evenly covered by PEG(8) and UFH-NHS. Both viability and functionality of islets were evaluated in vitro, and the anti-coagulation effect of conjugated heparin on the islet surface was also evaluated. The inhibition effects of PEG(8)/UFH double-layer shielding system on immune reactions and IBMIR induced by transplanted islets were evaluated in an allograft model. When pancreatic islets of Sprague-Dawley (SD) rats were transplanted in the liver of F344 rats, the mean survival time (MST) of PEG(8)/UFH double-layer shielded islets (6.8 ± 1.6 days) was statistically increased, compared to that of unmodified islets (3.6 ± 1.1 days). Furthermore, when 0.5 mg/kg of FK506 was daily administered, the MST of double-layer shielded islet (15.0 ± 2.1 days) was increased by two-fold, compared to that of unmodified islets treated with the same dose of FK506 (8.0 ± 2.4 days). Therefore, a newly developed strategy of combining the PEG(8)/UFH double-layer shielding system with FK506 would certainly be effective for preventing immune activation and IBMIR against allotransplanted islets.
authors.affiliation: Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Bok-Hyeon
authors.initials: BH
authors.lastname: Im
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Muhammad R
authors.initials: MR
authors.lastname: Haque
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
authors.forename: Ju Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy; D005215:Fasting / Q000097:blood; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D006493:Heparin / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013388:Succinimides / Q000737:chemistry; D016559:Tacrolimus / Q000737:chemistry / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D000925:Anticoagulants; D002396:Catechols; D007166:Immunosuppressive Agents; D007328:Insulin; D013388:Succinimides; D011092:Polyethylene Glycols; D006493:Heparin; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose; C034221:catechol; D016559:Tacrolimus