One promising approach for reducing the immune response to a transplant is that of gene therapy, whereby expression of particular genes involved in the immune system can be manipulated to alter the rejection response. In collaborative studies, we are using the harmless lentivirus to induce expression of a group of “protective” molecules on transplant tissues that will counteract the inflammatory immune response to transplantation. This study has been prompted by observations that these protective genes are naturally expressed on tissues that suffer an interrupted blood supply, such as happens during harvesting of the donor organ followed by re-establishing blood flow when the organ is implanted in the recipient. It is thought that the natural inflammatory response to the transplantation procedure contributes to the full-blown rejection response. Together with Prof Andrew Lever, we are testing the hypothesis that gene therapy to cause overexpression of protective genes will reduce the incidence of chronic rejection following transplantation. These studies would be helpful for human treatment since gene therapy using new-generation lentivirus as the agent is increasingly effective and safe.

There is also exciting new research that suggests there are stem cells in normal adults that have the role of repairing damaged tissues, such as donor kidneys that have had an interrupted blood supply. These cells, including mesenchymal stem cells and endothelial progenitor cells, are programmed to travel to the site of tissue injury but may also become damaged by the inflammatory environment once they get there. Our research is looking to see if we can provide the cells with protective genes that will help them survive the inflammation and be more effective at repairing the tissues.