Clinical translation of multipotent mesenchymal stromal cells in transplantation

The prevalence of chronic kidney disease and end-stage renal disease is increasing each year and currently the best therapeutic option for end-stage renal disease patients is kidney transplantation. However, although short-term graft outcomes after transplantation have improved substantially as a result of new and more potent immunosuppressive drugs, the long-term survival has hardly changed. This most likely is caused by a combination of nonimmunologic side effects and sustained alloreactivity to the graft resulting in fibrosis. In addition, current immunosuppressive drugs have side effects, including nephrotoxicity, infections, and malignancies that compromise long-term outcomes. Consequently, there is a strong interest in immunosuppressive therapies that maintain efficacy, while reducing side effects. Because mesenchymal stromal cells have potent anti-inflammatory and antifibrotic properties, these cells are of particular interest as new candidates in transplant recipients. Mesenchymal stromal cells might play roles in the treatment of allograft rejection and fibrosis and in calcineurin minimization and induction protocols. In the present review we discuss both preclinical as well as clinical evidence of their therapeutic potential in kidney transplantation. In addition, challenges and obstacles for clinical translation are discussed.