TY - JOUR
T1 - Allogeneic mesenchymal stromal cell therapy in kidney transplantation
T2 - should repeated human leukocyte antigen mismatches be avoided?
AU - Bezstarosti, Suzanne
AU - Erpicum, Pauline
AU - Maggipinto, Gianni
AU - Dreyer, Geertje J
AU - Reinders, Marlies E J
AU - Meziyerh, Soufian
AU - Roelen, Dave L
AU - De Fijter, Johan W
AU - Kers, Jesper
AU - Weekers, Laurent
AU - Beguin, Yves
AU - Jouret, François
AU - Heidt, Sebastiaan
N1 - Publisher Copyright:
Copyright © 2024 Bezstarosti, Erpicum, Maggipinto, Dreyer, Reinders, Meziyerh, Roelen, De Fijter, Kers, Weekers, Beguin, Jouret and Heidt.
PY - 2024/9/27
Y1 - 2024/9/27
N2 - Mesenchymal stromal cells (MSCs) have immunomodulatory properties and are therefore considered promising tools in kidney transplantation. Although most studies have been conducted with autologous MSCs, using allogeneic MSCs as an off-the-shelf product is more feasible in clinical settings. However, allogeneic MSCs could potentially induce an immune response, which might eventually be directed towards the kidney allograft because of shared human leukocyte antigen (HLA) epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analyses of two cohorts (n = 20) that received third-party MSC therapy after kidney transplantation. While the Neptune Study from Leiden University Medical Center specifically selected MSC to avoid repeated HLA antigen mismatches between kidney and MSC donors, the study from the University of Liège did not perform specific MSC selection. The comparative analyses of amino acid mismatches between these cohorts showed that MSC selection to avoid repeated HLA mismatches at the split antigen level was not sufficient to prevent repeated mismatches at the amino acid level. However, repeated amino acid mismatches were not associated with the occurrence of donor-specific antibodies (DSAs). Thus, the clinical relevance of repeated amino acid mismatches seems to be limited with regard to the risk of DSA formation. Since DSA formation was limited (3 of 20 patients) in this study, larger studies are required to investigate the relevance of preventing repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation.
AB - Mesenchymal stromal cells (MSCs) have immunomodulatory properties and are therefore considered promising tools in kidney transplantation. Although most studies have been conducted with autologous MSCs, using allogeneic MSCs as an off-the-shelf product is more feasible in clinical settings. However, allogeneic MSCs could potentially induce an immune response, which might eventually be directed towards the kidney allograft because of shared human leukocyte antigen (HLA) epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analyses of two cohorts (n = 20) that received third-party MSC therapy after kidney transplantation. While the Neptune Study from Leiden University Medical Center specifically selected MSC to avoid repeated HLA antigen mismatches between kidney and MSC donors, the study from the University of Liège did not perform specific MSC selection. The comparative analyses of amino acid mismatches between these cohorts showed that MSC selection to avoid repeated HLA mismatches at the split antigen level was not sufficient to prevent repeated mismatches at the amino acid level. However, repeated amino acid mismatches were not associated with the occurrence of donor-specific antibodies (DSAs). Thus, the clinical relevance of repeated amino acid mismatches seems to be limited with regard to the risk of DSA formation. Since DSA formation was limited (3 of 20 patients) in this study, larger studies are required to investigate the relevance of preventing repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation.
UR - http://www.scopus.com/inward/record.url?scp=85206359872&partnerID=8YFLogxK
U2 - 10.3389/fgene.2024.1436194
DO - 10.3389/fgene.2024.1436194
M3 - Article
C2 - 39399215
SN - 1664-8021
VL - 15
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 1436194
ER -