Use of small animal models for screening immunoisolation approaches to cellular transplantation.
It has been recognized for many years that immunoisolation strategies form an attractive approach to preventing the rejection of cellular allografts and xenografts. Although immunoisolation has proven dramatically successful in some cases, the results have tended to be somewhat variable. Although many advances have been made in the development of biocompatible materials for separating host immune cells from the transplanted tissues, much of the experimentation in this area has been outcome driven. That is, the nature of host reactivity and/or biomaterial design resulting in the failure of some immunoisolation strategies has mostly been undefined. A first premise of this discussion is that immunoisolation is primarily cell isolation and not antigen isolation, per se. That is, although varied membrane barriers are designed to prevent cell-cell contact between host and donor cells, soluble antigens derived from the transplant are likely to gain access to the host immune system. A key question centers on the degree and consequence of this type of antigen presentation in the host to the immunoisolated transplant. To address this and related concerns, this overview presents a simple paradigm for using defined rodent (mouse) models for systematically screening the efficacy of immunoisolated cellular transplants. The proposition is made that understanding the basis of graft failure will aid in the design of future immunoisolation technologies.
Gill
R G
RG
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA. ron.g.gill@uchsc.edu
D000818:Animals; D001672:Biocompatible Materials; D051379:Mice; D023421:Models, Animal; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000379:methods*
D001672:Biocompatible Materials