Performance of islets of Langerhans conformally coated via an emulsion cross-linking method in diabetic rodents and nonhuman primates
Aaron A. Stock, Grisell C. Gonzalez, Sophia I. Pete, Teresa De Toni, Dora M. Berman, Alexander Rabassa, Waldo Díaz, James C. Geary, Melissa A. Willman, Joy M. Jackson, Noa H. deHaseth, Noël Ziebarth, Anthony R. Hogan, Camillo Ricordi, Norma S. Kenyon, Alice A. Tomei
Abstract
Polyethylene glycol (PEG)-based conformal coating (CC) encapsulation of transplanted islets is a promising β cell replacement therapy for the treatment of type 1 diabetes without chronic immunosuppression because it minimizes capsule thickness, graft volume, and insulin secretion delay. However, we show here that our original CC method, the direct method, requiring exposure of islets to low pH levels and inclusion of viscosity enhancers during coating, severely affected the viability, scalability, and biocompatibility of CC islets in nonhuman primate preclinical models of type 1 diabetes. We therefore developed and validated in vitro and in vivo, in several small- and large-animal models of type 1 diabetes, an augmented CC method-emulsion method-that achieves hydrogel CCs around islets at physiological pH for improved cytocompatibility, with PEG hydrogels for increased biocompatibility and with fivefold increase in encapsulation throughput for enhanced scalability.