Biocompatibility Issues

Abstract

The possibility of transplanting cells in immunoprotective membranes for organ replacement dates back to 1933. At that time, Bisceglie (Bisceglie 1933) replaced the endogenous pancreas by transplanting insulin-producing tissue encapsulated in a semipermeable but immunoprotective membrane to study the effects of absence of vascularization on the survival of tissues. It took, however, until 1943 before the concept of immunoisolation was established by Algire (Algire 1943), who recognized that graft failure was delayed by encapsulating allo-and xenogenic tissues before transplantation. Algire was also the first to illustrate the importance of biocompatibility since he found that graft failure was always accompanied by cellular overgrowth of the membranes. At present, transplantation of cells in immunoisolating devices is under study for the treatment of a wide variety of diseases, including hemophilia B (Liu et al 1993), anemia (Koo and Chang 1993), dwarfism (Chang et al 1993), kidney (Cieslinski and Humes 1994) and liver (Uludag and Sefton 1993) failure, pituitary (Colton 1995) and central nervous system insufficiencies (Aebischer et al 1994), and diabetes mellitus (Lim and Sun 1980). When discussing biocompatibility aspects in this chapter, we will mainly focus on immunoisolation of pancreatic islets for the treatment of diabetes mellitus. We make this restriction for three reasons. The first is that most of the biocompatibility-related problems have been discovered in the application of immunoprotected insulin-producing cells, or the so-called bioartificial pancreas, probably as a consequence of the large number of groups involved in this type of research. Second, our own experience with biocompatibility research of immunoisolating capsules is mostly restricted to immunoprotected insulin-producing tissue. And third, most of the considerations regarding the biocompatibility of the bioartificial pancreas are also pertinent to other applications of immunoisolating devices.