Jonathan Lakey

By Michael Alexander, Huy Nguyen, Antonio Flores, Shiri Li, Paul De Vos, Elliot Botvinick and Jonathan Lakey

Islet transplantation, with the advent of the Edmonton protocol in 2000, has offered a significant alternative for long-lasting treatment of type 1 diabetes. However, the immunosuppression required for transplantation has the cytotoxic effect on pancreatic islets, and thus limiting the long-term efficacy of the transplant. Immediate loss of islets after transplant was also observed because of immediate blood-mediated inflammatory response (IBMIR), which kills islets transplanted in the liver through portal vein. There is also commonly a lack of microvascular blood supply to the transplanted islets. In this chapter, we will review the variety of technologies used to protect transplanted islets against toxicity of immunosuppression, immune rejection, and inflammatory response. We will evaluate the mechanisms of these technologies and their progress in solving the challenges to islet transplantation. The technologies include encapsulation of transplanted islets in various polymers, transplants in sites other than the liver, and creation of new prevascularized transplant site. These technologies offer several mechanisms to prevent immune rejection or immediate contact with cytotoxic inflammatory response, in addition to maintaining islet integrity. New transplant sites are also being developed to support the islets, by allowing establishment of microvasculature and innervation, prior to addition of the islets.

Part of the book: Challenges in Pancreatic Pathology

By Sarah Lee, Mayilone Sathialingam, Michael Alexander and Jonathan Lakey

Type 1 diabetes is an autoimmune disorder that destroys the insulin producing cells of the pancreas. The mainstay of treatment is replacement of insulin through injectable exogenous insulin. Improvements in islet isolation techniques and immunosuppression regimens have made islet transplants a treatment options for select patients. Islet transplants have improved graft function over the years, however, graft function beyond year two is rare and notably these patients require immunosuppression to prevent rejection. Cell encapsulation has been proposed for numerous cell types but it has found increasing enthusiasm for islets. Since islet transplants have experienced a myriad of success the next step is to improve graft function and avoid systemically toxic immunosuppressive regimens. Cell encapsulation hopes to accomplish this goal. Encapsulation involves encasing cells in a semipermeable biocompatible hydrogel that allows the passage of nutrients and oxygen however blocks immune regulators from destroying the cell thus avoiding systemic drugs. Several advances in encapsulation engineering and cell viability promises to make this a revolutionary discovery. In this chapter, we will provide a review of islet encapsulation as used for the treatment of type 1 diabetes.

Part of the book: Biomaterials

By Samuel Rodriguez, Rahul Tuli, Ashlyn Wheeler, Amy Nguyen, Jennifer Luong, Reza Mohammadi, Michael Alexander and Jonathan R.T. Lakey

Versatile yet biocompatible bio-materials are in high demand in nearly every industry, with biological and biomedical engineering relying heavily on common biomaterials like alginate polymers. Alginate is a very common substance found in various marine plants which can easily be extracted and purified through cheap nonhazardous methods. A key characteristic of alginate polymers includes easily manipulatable physical properties due to its inert but functional chemical composition. Factors including its functional versatility, long-term polymer stability and biocompatibility have caused alginate-based technologies to draw major attention from both the scientific and industrial communities alike. While also used in food industry manufacturing and standard dental procedures, this chapter will focus on a discussion of the both clinical and nonclinical use of alginate-based technologies in transplantation for regenerative cell and drug delivery systems. In addition, we overview the immune system response prompted following implantation of alginate hydrogels. Consequences of immune cell reactivity to foreign materials, such as inflammation and the foreign body response (FBR), are also analyzed and current and future strategies for potential circumvention of severe immune responses toward alginate-based devices are reviewed and suggested.

Part of the book: Alginates