Microencapsulation for Human Islet Transplantation

摘要

Encapsulation of islets is a promising strategy to deliver a cell therapy for treatment of type 1 diabetes without the need for anti-rejection drugs. The most common form of encapsulation is the microcapsule, which is made from sodium alginate, and is made robust by brief exposure to either Ca~(2+) or Ba~(2+). Transplantation of encapsulated human islets into diabetic immunodeficient mice results in rapid normalization of blood glucose levels. The number of encapsulated islets required to achieve normoglycemia is the same as the number of non-encapsulated islets. The minimal islet mass is 2000-3000 islet equivalents (IEQ), but this number can be reduced to 750-1000 IEQ if the encapsulated islets are pretreated overnight with 100μM desferrioxamine prior to transplantation. Transplantation of encapsulated islets into recipients with type 1 diabetes has been performed by several groups, with long term function of the grafts and a reduction of insulin requirements, but not insulin-independence, being demonstrated. A major issue that needs to be addressed to improve efficacy, is the prevention of pericapsular fibrotic overgrowth. This can lead to islet necrosis, as the pores that permit passage of nutrients and oxygen are obstructed. This overgrowth is caused by an inflammatory response to the encapsulation material and/or to antigens that leak through the pores. The peritoneal cavity seems not to be the best site for implantation, because of the large number of macrophages. Better survival is achieved in animals when encapsulated cells are grafted subcutaneously, but the low oxygen levels here limit the function of β cells since they thrive best at higher oxygen levels. An alternative to using microcapsules is the macrocapsule, but as yet there have been no human studies with islets examining its benefits. Reasons for continuing to pursue the use of encapsulated islets in the clinic are twofold. Firstly, they offer a potential means of overcoming the need for subcutaneous insulin administration without the need for anti-rejection drugs. Secondly, they lay the foundation for other forms of encapsulated allogeneic cell therapies, namely with stem cells or cells derived from them.