Mesenchymal Stem Cells in Organ Transplantation: Immunomodulatory properties of mesenchymal stem cells for application in organ transplantation

Abstract

Kidney transplantation is the only effective treatment for patients with end-stage renal disease. Transplantation of a donor organ, however, leads to recognition of the foreign donor antigens by the recipient’s immune system, resulting in rejection of the graft. In addition, ischemia-reperfusion injury leads to the initiation of immune responses. To prevent graft rejection, transplant recipients need to use life-long immunosuppressive medication. These drugs, however, can lead to serious acute and chronic side effects, such as infections, nephrotoxicity, cardiovascular disease and malignancies 1. As an alternative, cellular therapies may be considered. One of the candidates is the mesenchymal stem cell (MSC). Mesenchymal stem cells have tissue regenerative and immunosuppressive properties 2-4. These properties make them promising as cellular therapy for tissue regeneration and treatment of immunological disease. In solid organ transplantation, MSC may repair graft injury and may reduce anti-donor reactivity, thereby improving graft function and alleviating the need for immunosuppressive drugs after transplantation. Despite recent clinical trials investigating the use of MSC in treating immune-mediated disease, such as therapy resistant graft-versus-host disease (GVHD) and inflammatory bowel disease, the applicability of MSC in solid organ transplantation is still unknown. The present thesis discusses the immunomodulatory properties of MSC and their potential to improve the outcome of solid organ transplantation