title: Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: the neptune study.
abstract: BACKGROUND
  Mesenchymal stromal cells (MSC) may serve as an attractive therapy in renal transplantation due to their immunosuppressive and reparative properties. While most studies have used autologous MSCs, allogeneic MSCs offer the advantage of immediate availability for clinical use. This is of major importance for indications where instant treatment is needed, for example allograft rejection or calcineurin inhibitor toxicity. Clinical studies using allogeneic MSCs are limited in number. Although these studies showed no adverse reactions, allogeneic MSCs could possibly elicit an anti-donor immune response, which may increase the incidence of rejection and impact the allograft survival in the long term. These safety issues should be addressed before further studies are planned with allogeneic MSCs in the solid organ transplant setting.
  
  
  METHODS
  10 renal allograft recipients, 18-75 years old, will be included in this clinical phase Ib, open label, single center study. Patients will receive two doses of 1.5 × 10(6) per/kg body weight allogeneic bone marrow derived MSCs intravenously, at 25 and 26 weeks after transplantation, when immune suppression levels are reduced. The primary end point of this study is safety by assessing biopsy proven acute rejection (BPAR)/graft loss after MSC treatment. Secondary end points, all measured before and after MSC infusions, include: comparison of fibrosis in renal biopsy by quantitative Sirius Red scoring; de novo HLA antibody development and extensive immune monitoring; renal function measured by cGFR and iohexol clearance; CMV and BK infection and other opportunistic infections.
  
  
  CONCLUSIONS
  This study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss.
  
  
  BACKGROUND
  NCT02387151.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. m.e.j.reinders@lumc.nl.
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. G.J.Dreyer@lumc.nl.
authors.forename: Geertje J
authors.initials: GJ
authors.lastname: Dreyer
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. J.R.Bank@lumc.nl.
authors.forename: Jonna R
authors.initials: JR
authors.lastname: Bank
authors.affiliation: Department of Immuno-Haematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. H.Roelofs@lumc.nl.
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.affiliation: Department of Immuno-Haematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. S.Heidt@lumc.nl.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Heidt
authors.affiliation: Department of Immuno-Haematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. D.L.Roelen@lumc.nl.
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.affiliation: Department of Clinical Parmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. M.L.Zandvliet@lumc.nl.
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Zandvliet
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. V.A.L.Huurman@lumc.nl.
authors.forename: Volkert A L
authors.initials: VA
authors.lastname: Huurman
authors.affiliation: Department of Immuno-Haematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. W.E.Fibbe@lumc.nl.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Fibbe
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. C.van_Kooten@lumc.nl.
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.affiliation: Department of Immuno-Haematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. F.H.J.Claas@lumc.nl.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. A.J.Rabelink@lumc.nl.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. A.J.Rabelink@lumc.nl.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. J.W.de_Fijter@lumc.nl.
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D001854:Bone Marrow Cells / Q000166:cytology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D066027:Transplant Recipients; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents