The lack of availability of organs for transplantation is currently the limiting resource in clinical organ transplantation in the late 1980's. One viable alternative to increase the numbers of organs for transplantation is to develop successful cross-species transplantation, i.e., xenotransplantation. A model providing for successful prolongation of xenograft survival has been developed. This model utilizes the harshest xenograft combination pig to dog transplantation, in order to further identify interventions allowing significant prolongation of xenograft survival. The ultimate application would be to utilize these modifications and alterations to allow the human clinical use of xenotransplants. This model uses the donor-specific depletion of antibodies in the dog recipient by plasmapheresis and subsequent ex vivo antibody adsorption via perfusion of the donor animal's organ. The donor animal's adsorbing organ (spleen, liver, kidney) is harvested and perfused in an ex vivo fashion with the cell free plasma from the recipient, and the effluent from that organ is returned to the recipient animal. It appears that formed elements are necessary for initiating and completing the destruction of xenografts. As a result, the ex vivo perfused donor organ does not undergo hyperacute rejection and therefore allows ongoing, prolonged perfusion of the donor organ and its associated endothelial bed with subsequent binding of destructive xenoantibodies. Preliminary evidence has demonstrated prolongation from the control survival of approximately 8 minutes to survival times of well over three hours in the modified recipient. This proposal addresses further study with this model, including: 1) refinement of the model system, 2) improving the efficacy of antibody adsorption by manipulation of various adsorbing organs, 3) further characterization of the offending xenoantibody, 4) dissection of various component parts of the xenoresponse as it pertains to the formed elements found in the recipient, and 5) combining both antibody depletion and inhibition of mediators of the xenoresponse.
| Henry, M L; Bendle, M D; Ferguson, R M (1994) Leukocyte inhibition and ex vivo whole blood xenoperfusion. Transplant Proc 26:1311 |
| Henry, M L; Bendle, M D; Bryan, B A et al. (1994) Antibody depletion and blockage of adhesion molecules prolongs renal xenograft survival in the pig to dog model. Transplant Proc 26:1362 |
| Henry, M L; Han, L K; Davies, E A et al. (1994) Antibody depletion prolongs xenograft survival. Surgery 115:355-61 |
| Bryan, B A; Henry, M L; Ferguson, R M (1992) Prolongation of renal xenograft survival by calcium sequestration. Transplant Proc 24:699 |
| Bryan, B A; Henry, M L; Ferguson, R M (1992) Renal xenografts perfused ex vivo require both humoral and cellular components to undergo hyperacute rejection. Transplant Proc 24:609 |
| Bryan, B A; Henry, M L; Ferguson, R M (1992) Neutrophils attenuate thrombus formation in renal xenografts perfused ex vivo. Transplant Proc 24:436 |
