Gene Therapy for Heart Transplantation-Associated Acute Rejection, Ischemia / Reperfusion Injury and Coronary Arteriosclerosis

Mitsuaki      Isobe; Hisanori      Kosuge; Noritaka      Koga; Hideki      Futamatsu; Jun-ichi      Suzuki

Abstract

Acute cardiac allograft rejection is still a major complication after heart transplantation. Acute rejection usually responds to conventional immunosuppressions, however, the nonspecific nature of the immunosuppression and the toxicities of the drugs can be life threatening and may compromise the recipients quality of life. In addition, cardiac allograft arteriosclerosis or chronic rejection limits the long-term survival of recipients. Such conditions cannot be prevented with conventional therapies. To overcome acute and chronic rejection of cardiac allograft as well as ischemia / reperfusion injury associated with organ preservation many novel approaches have been proposed. Gene transfection of the donor organ during organ preservation is an attractive method, because the transfected genes would not affect recipients and treatment could be delivered specifically to the site of inflammation. This method could be useful to prevent graft failure without systemic adverse effects. Here we shall review current advances in gene therapies to prevent and treat organ failure of transplanted allografts.

Keywords: acute rejection, chronic rejection, gene therapy, graft vasculopathy, heart transplantation, immunosuppression, ischemia/reperfusion injury, tolerance