Encapsulation Strategies for Pancreatic Islet Transplantation without Immune Suppression

Purpose of Study Although the current treatment option of exogenous insulin administration for type 1 diabetes mellitus (T1DM) corrects hyperglycemia, it has its own limitations and complications in long-term use. Thus, alternative approaches such as immune therapies, glucose transporter inhibitors, gastro-enteric protein-hormone pathway modulators, and cell- and tissue-based therapies are being developed. Among these therapies, islet transplantation has been shown to be a more physiological means of treating type 1 diabetes. However, the shortage of donor tissues and the use of immunosuppressive agents have led to the development of immune isolation techniques such as cell encapsulation. Recent findings Although macroencapsulation of islets has been shown with some success, microencapsulation mostly with permselectively coated alginate hydrogel has been demonstrated to be superior among the variety of developed encapsulation technologies including nanoencapsulation and thus, has led to several clinical trials. While microencapsulated islet transplantation has shown promise in correcting the pathological symptoms of T1DM, the technology still requires improvement in a few areas in order to achieve sustained performance in long-term application. Summary Some approaches suggested for improvement include incorporation of immunomodulatory stem cells such as mesenchymal stem cells, substitution of current crosslinking agents with stable safe divalent cations, improving the chemistry of alginate by adding functional groups, and including extracellular matrix (ECM) components of the pancreas in the encapsulated islet construct. With thorough investigation and improvement on the pitfalls of the technology, and more clinical trials, the microencapsulation technology would provide a viable option for a sustainable and more physiological means of insulin delivery in T1DM.