Collaborators provide the biology component of the program project. This includes analysis of HS-based therapies in mice and pigs. The HS-based molecules developed in Projects I and II will be tested in vitro to determine the best HS candidate drugs for further studies followed by ex vivo pig lung hemoperfusion using human blood.
Alternatively, molecules developed in Projects I and II may be evaluated in mice models of thrombosis including FeCl3 and Rose Bengal models. Potentially interesting molecules will also be analyzed in pig artery Tx in baboons and pig kidney Tx in baboons. The effect of the HSs will be monitored (iii) in a low-antigen load model without immunosuppressive therapy, or (iv) in a high-antigen load model in which graft recipients will receive immunosuppressive therapy aimed at inhibiting the adaptive T cell response.