AUTHOR=Dreyer Geertje J. , Drabbels Jos JM. , de Fijter Johan W. , van Kooten Cees , Reinders Marlies EJ. , Heidt Sebastiaan 

TITLE=Cell-free DNA measurement of three genomes after allogeneic MSC therapy in kidney transplant recipients indicates early cell death of infused MSC

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1240347

DOI=10.3389/fimmu.2023.1240347

ISSN=1664-3224

ABSTRACT=Mesenchymal stromal cell (MSC) therapy is a promising treatment to allow for drug minimization in clinical kidney transplantation. While it is thought that MSCs rapidly go into apoptosis after infusion, clinical evidence for this is scarce, since methods to detect cell death of infused cells in vivo are lacking. Cell-free DNA (cfDNA) has recently gained attention to serve as a biomarker for cell death. In this study we longitudinally measured cfDNA in plasma samples of the recipient, kidney donor and allogeneic third party MSC in context of the Neptune study. cfDNA levels were measured at several time points before and after allogeneic MSC infusion in the 10 recipients who participated in the Neptune study. cfDNA ratios between recipient, kidney graft and MSC were determined. We observed a peak in MSC derived cfDNA at four hours after the first and second infusion after which MSC derived cfDNA became undetectable. Generally, kidney graft derived cfDNA remained at baseline level range.Our results support preclinical data that MSC are short lived after infusion also in a clinical in vivo setting and are relevant for further research into the mechanism of action of MSC therapy.