Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice.
Sigmundsson K., Ojala JRM., Öhman MK., Österholm A-M., Moreno-Moral A., Domogatskaya A., Chong LY., Sun Y., Chai X., Steele JAM., George B., Patarroyo M., Nilsson A-S., Rodin S., Ghosh S., Stevens MM., Petretto E., Tryggvason K.
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.