Engineering β-cell islets or islet-like structures for type 1 diabetes treatment

Type 1 diabetes mellitus is a disease characterized by the destruction of the β-cells in the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is insulin injections administered multiple times throughout the day. However, this treatment cannot provide sustained physiological release of insulin and the insulin amount is not finely tuned to the glycemia condition. Pancreatic transplantation or islet transplantation would be the preferred treatment strategy but the lack of donor tissue and immunoincompatibility has been shown to be a roadblock to their widespread use. Bioengineering strategies are poised to combat these challenges. Islet encapsulation is expected to offer both immunoisolation and immunomodulation effects by: (1) physically protecting islets from the attacks of immunoglobulins, complements, and host immune cells, and (2) delivering immune regulatory and immunomodulatory factors locally to the islets to protect those islets from immune rejection. Semi-permeable coatings using biocompatible biomaterials can be used for immunoisolating islets away from the host immune systems. Immunoisolation technology also provides an opportunity to use other cell sources for cell therapy to treat type 1 diabetes. Recently, some studies reported that co-transplantation of islets with mesenchymal stem cells (MSCs) can control graft inflammation. MSCs have immunomodulatory property. They are able to secrete anti-inflammatory factors and repress the activity of various immune cells. Growth factors like interleukin 10 (IL-10) and leukemia inhibitory factor (LIF) also have immune regulatory properties. Therefore immunoisolation and immunomodulation technologies can be integrated and applied to β-cell encapsulation for the treatment of type 1 diabetes. Through engineering β-cell islets or islet-like microtissues, the viability and function of transplanted β-cells may be improved. In the meantime, the survival of transplanted β-cells can be further improved by promoting vascular network formation surrounding the transplanted islets or microtissues.