Study Design
CREST
The TRITON clinical trial was a randomized phase II, prospective, single-center, open-label study in living-donor kidney transplant recipients in which autologous bone marrow derived MSC therapy, with concomitant early tacrolimus withdrawal, was compared to standard tacrolimus dosing. The study was performed at the Leiden University Medical Center (LUMC), the Netherlands. The trial design and trial protocol have been previously described and were approved by the local ethics committee at the LUMC, Leiden, and by the Central Committee on Research involving Human Subjects in the Netherlands [In short, patients in the MSC group received two doses of autologous bone marrow derived MSCs, intravenously at weeks 6 and 7 after transplantation. Bone marrow was aspirated from the posterior iliac crest of all patients in the MSC group during the renal transplantation. Processing of the MSCs took place at the GMP Facility of the LUMC. The MSC product was infused at week 6 and week 7 via peripheral infusion within 30 min with a target dose of 1.5 × 106 per/kg body weight intra venously (range 1–2 × 10During the trial, protocol blood samples were obtained before transplantation (week 0), at weeks 6, 12, 24 and 52 after transplantation. Of the 70 subjects, 34 were selected for the mass cytometry study of which 21 had received MSC treatment and 13 were control patients. Selection was based on the availability of sufficient PBMCs, a 3:2 ratio between the MSC group and control group and similar age distribution (control; 26–66 years, mean: 50 years, MSC; 31–70 years, mean: 51 years), All patients received their allocated treatment. In the control group one patient had not enough PBMCs stored at 24 weeks and another patient lacked the 52 weeks timepoint. Limited immune phenotyping by flow cytometry was already performed on fresh PBMCs of these patients and showed several differences at 24 and 52 weeks [