Novel siRNA-Containing Solution Protecting Donor Organs in Transplantation
Donor organs are subjected to flushing and storage in hypothermic conditions (4 ?C) in specially formulated solutions (organ storage solutions) in order to wash out debris and to decrease damage during transportation 1. Such solutions can be broadly differentiated into “extracellular” and “intracellular” based on the physiological milieu they mimic. Two typical solutions are the University of Wisconsin (UW)-solution (intracellular) and the Celsior solution (extracellular) 2, with the latter being optimized for cardiac preservation 3. Both of these solutions contain active components which: 1) Minimize cell swelling caused by hypothermia; 2) Inhibit acidosis due to ischemia; 3) Minimize extracellular expansion; 4) Prevent free-radical damage; and 5) Supply a substrate for regenerating ATP during reperfusion 4. A variety of groups have performed modifications to typical perfusion solutions to attain better graft function. Addition of free-radical protectors such as vitamin E or ascorbate to UW solution resulted in an increased donor organ survival 5,6. Protection of parenchymal tissue by incorporation of caspase inhibitors was also demonstrated 7. Addition of angiotesin converting enzyme inhibitors to storage solution marginally increased function of the donor hearts 8. Despite these modifications, little work has been performed on altering immunogenicity the organ, which directly related to graft rejection. ToleroTech developed a type of new siRNA-containing solution that can significantly prolong the preservation time, protect cardiac function, and prolong graft survival in heart transplantation, implying a significant and potential application in the clinical transplantation.
