Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: The neptune study

Marlies E.J. Reinders, Geertje J. Dreyer*, Jonna R. Bank, Helene Roelofs, Sebastiaan Heidt, Dave L. Roelen, Maarten L. Zandvliet, Volkert A.L. Huurman, Wim E. Fibbe, Cees Kooten, Frans H.J. Claas, Ton J. Rabelink, Johan W. de Fijter

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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/design: 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 × 106 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. Discussion: This study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss.

Original languageEnglish
Article number344
JournalJournal of Translational Medicine
Volume13
Issue number1
DOIs
Publication statusPublished - 4 Nov 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Reinders et al.

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