Creating a 3D matricellular environment to promote islet expansion for diabetes therapy – the role of SPARC family proteins

Abstract

Loss of the extracellular matrix following enzyme harvest of islets for transplantation renders them susceptible to a new environment, and is hypothesized to contribute to decreased graft function and survival. The matrix provides structural support for islets as well as mediating growth factor and cytokine interactions. SPARC, or secreted protein acidic and rich in cysteine, is a collagen‐binding matricellular protein that plays a role in matrix assembly and regulates cellular responses to the extracellular environment. Our data shows that SPARC is expressed by stromal cells within islets, and that SPARC expression in these cells is regulated by metabolic factors. Furthermore, SPARC inhibits growth factor signalling in both beta cells and primary islet tissue. Our data suggests that understanding the effect of matricellular proteins will be necessary to create a matrix environment that supports islet expansion. We have developed a model in which matricellular protiens are incorporated into a 3D collagen matrix to test the effect of matricellular proteins on primary islet growth and survival.