Requirements for Encapsulation Technology and the Challenges for Transplantation of Islets of Langerhans

Abstract

Requirements for successful cellular encapsulation are reviewed, with emphasis on the bioartificial pancreas. These requirements fall into three general categories: graft tissue viability, host response, and surgical practicality. Several design decisions, such as choice of materials, have ramifications on many requirements that must be simultaneously considered. Device dimensions are critical for allowing sufficient oxygen flux to the graft tissue. Host response to the materials used is varied. Some materials appear to promote new blood vessel growth, yet evidence distinguishing genuine neovasculariza-tion from ongoing fibrosis is scant. A neutral host response is supported by the authors' work, which additionally increases the possibility of device retrieval. The use of alginates for bioneutral encapsulation has mixed results, possibly because the polymer properties and the purity of the alginates are rarely characterized. Polycations, such as polyly-sine, have been applied to overcome shortcomings in polymer chemistry but have been shown to be unnecessary and possibly detrimental to host response. Microcapsules often suffer from incomplete coverage of cells, another issue that is rarely addressed. Complete coverage is an absolute requirement for evasion of humoral immune destruction of the encapsulated tissue. Introduction Implantation of secretory cells encapsulated to prevent host rejection is an appealing concept with a long experimental history but minimal clinical success. The exemplary bioartificial pancreas is the one containing insulin-producing islets of Langer-hans, for which there is a great clinical need in the treatment of insulin-requiring diabetes. Many other cells and tissues are also attractive candidates for encapsulation, including cells to reverse endocrine deficiencies, or which produce therapeutic biolog-ics. In this brief review, we focus only on the bioar-tificial pancreas. Recent advances in transplantation of islets of Langerhans by the Edmonton group 1 have demonstrated that the rate of islet transplant success, defined as freedom from insulin injections, can be as high as solid organ such as kidney transplants. The