Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice

Sigmundsson K., Ojala J.R.M., Öhman M.K. Österholm A-M., Moreno-Moral A., Domogatskaya A., Yen Chong L., Sun Y., Chai X., Steele J.A.M, George B., Patarroyo M., Nilsson A-S., Rodin S., Ghosh S., Stevens M.M., Petretto E., Tryggvason K.

Matrix Biology, 2018

Here, the authors have developed a novel method to grow and maintain normoxic and functional islets which may significantly enhance the efficacy of islet transplantation treatment for diabetes. A key component of this method is the coating with biologically relevant laminins, found in the peri-islet capsule and BM of islet capillaries. Islets cultured in vitro on α5-laminins adhere and spread to form layers of 1-3 cells in thickness while maintaining cell-to-cell contacts. The cells 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 hours. Mouse islets plated on laminin-521 could be cultured in a serum-free mTeSR1 medium for an extended period of time. Approximately 20% of islet cells showed a co-expression of insulin and glucagon. The double-hormone expression was confirmed in histological analyses of mouse and monkey pancreata. The flattened islets start robust cell proliferation after a lag period of approximately two weeks in a serum-free mTeSR1 culture on laminin-521. Transplantation 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.