David H. Sachs, MD
Paul S. Russell/Warner Lambert Professor of Surgery, Department of Surgery, Harvard Medical School
Scientific Director, Transplantation Biology Research Center, Massachusetts General Hospital
DF/HCC Program AffiliationCancer Immunology
Our laboratory utilizes partially inbred miniature swine as a large animal pre-clinical model and as potential donors for organ xenotransplantation. Three herds of miniature swine homozygous for different sets of histocompatibility antigens at the major histocompatibility complex (MHC) have been developed by the principal investigator over the past 30 years. These animals show many similarities to humans both immunologically and physiologically and are of similar size to humans, facilitating their potential use as xenograft donors. In addition, five different intra-MHC recombinants have been isolated and bred to homozygosity, making this the only large animal model in which immunogenetic studies of the MHC and its role in transplantation can be performed reproducibly. Our current projects include: 1) Assessment of the effect of selective MHC matching on the survival of organ and tissue transplants: Studies are carried out in vivo and in vitro assessing the mechanism of rejection and induction of transplantation tolerance across selective MHC barriers; 2) Production and characterization of monoclonal antibodies reactive with subsets of pig lymphocytes; 3) Bone marrow transplants in miniature swine: The effect of treatment regimens to mitigate Graft-versus-Host disease (GVHD) and the use of bone marrow transplantation as a means for inducing specific transplantation tolerance across MHC barriers are being studied; 4) Studies of porcine to primate xenografts: Attempts are under way to extend our previous studies on induction of specific tolerance across concordant species barriers (rat to mouse and baboon to monkey) to the discordant xenograft system (pig to baboon). Induction of tolerance is tested by organ xenografts. Major collaborative studies within the TBRC and between the TBRC and the Transplant Unit of the Surgery Department are carried out.
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