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The Annals of Thoracic Surgery, Vol 56, 1221-1227, Copyright © 1993 by The Society of Thoracic Surgeons
DH Sachs
Two major factors currently limiting the field of transplantation are (1)
treatment-related complications and (2) donor organ availability. This
article reviews progress from our laboratory in research directed at
solutions to both of these limitations. The induction of specific tolerance
could eliminate many of the treatment-related complications currently
attributable to nonspecific immunosuppressive drug therapy. The methodology
being investigated involves use of mixed chimerism as an approach to
transplantation tolerance. In this case, the presence of certain donor bone
marrow-derived elements induces specific tolerance, whereas host-type
antigen presenting cells confer normal immunocompetence. In addition,
extension of this work toward tolerance across xenogeneic barriers could
eliminate the limitation of organ donor availability. A nonmyeloablative
preparative regimen capable of inducing mixed chimerism and tolerance has
previously been described from our laboratory for both allogeneic murine
systems and concordant xenogeneic rat-->mouse systems. Current studies
attempting to extend this regimen to a discordant pig-->monkey xenograft
model are reviewed. If successful, these studies could provide a virtually
limitless source of xenogeneic donor organs.
ARTICLES
CCETS Basic Science Lecture. Transplantation tolerance
Harvard Medical School, Boston, Massachusetts.
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