title: Islet surface modification with urokinase through DNA hybridization.
abstract: Transplantation of islets of Langerhans (islets) has been proposed as a safe, effective approach to treating patients with insulin-dependent diabetes mellitus (type I diabetes). It has been reported, however, that many islets are lost in the early phase after intraportal transplantation by instant blood coagulation-mediated inflammatory reactions. In this study, DNA hybridization was applied to conjugate the fibrinolytic enzyme urokinase on the islet surface. We synthesized amphiphilic polymers, PEG-lipids carrying oligo(dT)(20) (oligo(dT)(20)-PEG-lipid; PEG MW = 5000) and urokinase (UK) carrying oligo(dA)(20). The oligo(dT)(20)-PEG-lipid was spontaneously incorporated into the cell membrane through interactions between the hydrophobic parts of the PEG-lipids and the lipid bilayer, and UK was conjugated on the cell surface through DNA hybridization between oligo(dT)(20) on the cell and complementary oligo(dA)(20) on the UK. The activity of UK was maintained on the islet surface. The surface modification with UK did not influence islet morphology or islet ability to secrete insulin in response to changes in glucose concentration. No practical volume increase was observed with our method, indicating that islet graft loss could be suppressed at the early stage of intraportal islet transplantation.
authors.affiliation: Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University , 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Takemoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Teramura
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007515:Islets of Langerhans / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D009838:Oligodeoxyribonucleotides; D011092:Polyethylene Glycols; D014568:Urokinase-Type Plasminogen Activator