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

Matrix Biol. 2018 Sep;70:5-19. doi: 10.1016/j.matbio.2018.03.018. Epub 2018 Mar 27.

Abstract

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.

Keywords: Diabetes; Islet; Laminin; Pancreatic; Transplantation; β-cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cell Culture Techniques*
  • Cell Proliferation
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / surgery
  • Diabetes Mellitus, Experimental / therapy*
  • Extracellular Matrix / chemistry
  • Humans
  • Insulin / biosynthesis
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / surgery
  • Islets of Langerhans Transplantation*
  • Laminin / chemistry*
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Streptozocin
  • Treatment Outcome

Substances

  • Blood Glucose
  • Insulin
  • Laminin
  • laminin alpha5
  • Streptozocin