Immobilization of urokinase on the islet surface by amphiphilic poly(vinyl alcohol) that carries alkyl side chains

Abstract

Transplantation of islets of Langerhans (islets) is a promising method to treat insulin-dependent diabetes mellitus (type I diabetes). However, insulin independence is typically realized for only ∼30% of transplant recipients, even with sufficient numbers of islets from multiple donors. Innate immunological reactions triggered by blood coagulation play a key role in the loss of islets at the early stage. Here we propose a method to inhibit blood coagulation on the islet surface. A plasminogen activator, urokinase, was immobilized on the islet surface via a poly(vinyl alcohol) (PVA) derivative that carries alkyl chains and thiol groups. When the PVA derivative was added to an islet suspension, the alkyl side chains spontaneously anchored into the lipid bilayer membranes of islet cells. The surfaces of islets were covered with the PVA derivative. Urokinase modified with maleimide groups could be immobilized onto the islet surface by thiol/maleimide bonding with the layer of PVA derivatives. Urokinase-immobilized islets exhibited fibrinolytic properties, indicating that blood coagulation can be controlled on the islet surface. Urokinase immobilization on islets, which does not impair insulin release, represents a promising method to reduce early graft loss after intraportal islet transplantation.