title: Clinical translation of multipotent mesenchymal stromal cells in transplantation.
abstract: 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.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Daniëlle G
authors.initials: DG
authors.lastname: Leuning
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: de Fijter
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: t.rabelink@lumc.nl.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
mesh_terms: D000818:Animals; D005355:Fibrosis; D006084:Graft Rejection / Q000517:prevention & control* / Q000628:therapy; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells
chemical_list: D007166:Immunosuppressive Agents
keywords: Mesenchymal stromal cells; immunomodulation; kidney transplantation; renal disease; repair