A tissue engineering approach towards treatment of type 1 diabetes

Abstract

Transplanting islets into a patient's portal vein is currently the most promising method to treat type one diabetes. However, the long-term efficiency of this method has only been demonstrated in a small number of the treated patients. In the majority of patients, the treatment ultimately fails and they will still suffer from labile blood glucose control. Although it is known that multiple factors play an important role in the loss of donor cells, such as the immediate blood mediated inflammatory response, allo and auto immune reaction, poor revascularization and high levels of glucose, lipids and immunosuppressive drugs. Another factor, which more recently is being studied, is the effect of islet isolation, which can induced damage to the β-cell's microenvironment. Specifically, in order to isolate islets the pancreas is perfused with collagenase, this leads to enzymatic digestion of the islets extra cellular matrix causing loss of the general extracellular matrix (ECM) network architecture, and supportive ECM molecules. Another important factor, is insufficient rapid vascularization after transplantation leading to poor mass transport of oxygen and nutrients to the metabolically very active β-cells leading to cell stress, apoptosis and loss of function. The ECM in islets consists predominantly of a basement membrane associated with the dense microvasculature surrounding the endocrine cells. Consequently, it is expected that islet transplantation can be significantly improved by re-establishing the islet microenvironment. Here, we review the state-of-the-art in engineering islet microenvironments, and provide a comprehensive understanding of the relationship between pancreatic islet cells and its surrounding microenvironment within the islet. Additionally, we highlight the progress and challenges related to the biological, biochemical, and biophysical aspects of engineering the islet micro-environment for transplantation purposes.