Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, USA
Address for correspondence: Ronald G. Gill, Ph.D., Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Ave., Box B-140, Denver, CO 80262, USA. Voice: 303-315-6390; fax: 303-315-4124.
ron.g.gill{at}uchsc.edu
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.
