Human leukocyte antigen selected allogeneic mesenchymal stromal cell therapy in renal transplantation: The Neptune study, a phase I single-center study

Geertje J. Dreyer*, Koen E. Groeneweg, Sebastiaan Heidt, Dave L. Roelen, Melissa van Pel, Helene Roelofs, Volkert A.L. Huurman, Ingeborg M. Bajema, Dirk Jan A.R. Moes, Willem E. Fibbe, Frans H.J. Claas, Cees van Kooten, Rabelink J. Rabelink, Johan W. de Fijter, Marlies E.J. Reinders

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Scopus)
7 Downloads (Pure)

Abstract

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, although with 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 1.5 × 106/kg allogeneic MSCs 6 months after transplantation in a single-center nonrandomized phase Ib trial, followed by lowering of tacrolimus (trough level 3 ng/mL) in combination with everolimus and prednisone. Primary end point 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 the efficacy of third-party MSCs in renal transplantation.

Original languageEnglish
Pages (from-to)2905-2915
Number of pages11
JournalAmerican Journal of Transplantation
Volume20
Issue number10
Early online date10 Apr 2020
DOIs
Publication statusPublished - Oct 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons

Fingerprint

Dive into the research topics of 'Human leukocyte antigen selected allogeneic mesenchymal stromal cell therapy in renal transplantation: The Neptune study, a phase I single-center study'. Together they form a unique fingerprint.

Cite this