Culturing functional pancreatic islets on a5-laminins and curative transplantation to diabetic mice

• Published in: Matrix biology 2018-09, Vol.70, p.5
• Main Authors: Sigmundsson, Kristmundur, Ojala, Juha R M, Öhman, Miina K, Österholm, Anne­May, MorenoMoral, Aida, Domogatskaya, Anna, Chong, Li Yen, Sun, Yang, Chai, Xiaoran, Steele, Joseph A M, George, Benjamin, Patarroyo, Manuel, Nilsson, Ann­Sofie, Rodin, Sergey, Ghosh, Sujoy, Stevens, Molly M, Petretto, Enrico, Tryggvason, Karl
• Format: Article
• Language: English
• Subjects: Basement membranes; Cell culture; Diabetes; Diabetes mellitus; Hypoxia; Islet cells; Laminin; Medical treatment; Necrosis; Pancreas transplantation; Pancreatic islet transplantation; Polydimethylsiloxane; Ribonucleic acid; RNA; Rodents; Streptozocin; Transplants & implants
• ISSN: 0945-053X; 1569-1802

The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1–3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110–150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3–7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.