Human Leukocyte Antigen Selected Allogeneic Mesenchymal Stromal Cell Therapy in Renal Transplantation: the Neptune study, a phase I single-center study.

Mesenchymal stromal cells (MSC) hold promise as a novel immune-modulatory therapy in organ transplantation. First clinical studies have used autologous MSCs, however the use of allogeneic 'off-the-shelf' MSCs is more sustainable for broad clinical implementation however has the risk of causing sensitization. We investigated safety and feasibility of allogeneic MSCs in renal transplantation, using a matching strategy that prevented repeated mismatches. Ten patients received two doses of 1.5x10(6) /kg allogeneic MSCs 6 months after transplantation in a single-center non-randomized phase Ib trial, followed by lowering of tacrolimus (trough level 3 ng/ml) in combination with everolimus and prednisone. Primary endpoint was safety, measured by biopsy proven acute rejection (BPAR) and graft loss 12 months after transplantation. Immune monitoring was performed before and after infusion. No BPAR or graft loss occurred and renal function remained stable. One patient retrospectively had DSAs against MSCs, formed before infusion. No major alterations in T- and B-cell populations or plasma cytokines were observed upon MSC infusion. Administration of HLA selected allogeneic MSCs combined with low dose tacrolimus 6 months after transplantation is safe at least in the first year after renal transplantation. This sets the stage to further explore efficacy of third-party MSCs in renal transplantation.