Autologous Mesenchymal Stem Cells for Treatment of Chronic Antibody-Mediated Kidney Graft Rejection: Report of the First Phase I/II Clinical Case Series
1Nephrology, UMC Ljubljans, Ljubljana, Slovenia, 2Haematology, UMC Ljubljans, Ljubljana, Slovenia, 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana,, Ljubljana, Slovenia, 4Division of Nephrology and Transplant Immunology, University of Alberta, Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada, 5University Medical Centre Ljubljana, Ljubljana, Slovenia
Meeting: 2022 American Transplant Congress
Abstract number: 177
Keywords: Bone marrow, Graft failure, Rejection
Topic: Basic Science » Basic Science » 05 - Translational Cellular Therapies: Islet and Stem Cell Transplantation
Session Information
Session Name: Cellular/Islet Therapies and Tissue Engineering
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 5, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 5:40pm-5:50pm
Location: Hynes Room 310
*Purpose: The aim of this study is to evaluate the safety and efficacy of autologous mesenchymal stem cellc (MSCs) in combination with standard of care therapy in patients with biopsy-proven chronic antibody-mediated rejection (cAMR).
*Methods: In this prospective, interventional single-center study (ClinicalTrials.gov, number NCT03585855), patients with biopsy-proven cAMR were offered treatment with autologous bone marrow MSCs (3×106 cells/kg iv) after completion of standard of care therapy (including corticosteroids, membrane plasmapheresis, and intravenous immunoglobulins). Patients underwent prior bone marrow aspiration and were followed up regularly up to 24 months’ post MSCs therapy. The primary endpoints were safety by assessment of allograft loss and adverse events according to CTCAE. Secondary endpoints of the study included assessment of kidney function and histological changes in the allograft associated with cAMR activity and chronicity assessed by conventional microscopy, Banff scores and molecular transcripts (Molecular Microscopy Diagnostic System – MMDx).
*Results: A total of 3 patients were enrolled in the study before it was terminated prematurely due to life-threatening side effects. Patient#1 experienced no MSCs-related side effects, patient#2 experienced non-infectious diarrhoea after the second MSCs dose and further treatment was discontinued. Patient#3 experienced serious adverse effects and allograft loss 2 months after MSCs treatment. A 24-month follow-up in patient#1 and patient#2 showed progressive deterioration of kidney allograft function with increasing proteinuria. Conventional and molecular histology performed 12 months after treatment with MSCs failed to demonstrate improvement in cAMR. Expression of miRNAs associated with AMR was not affected by treatment with MSCs.
*Conclusions: This is the first study using autologous MSCs to cure cAMR in kidney allograft recipients. In our very limited study, cAMR did not improve in any of the patients after treatment with MSCs. Moreover, in this case, when autologous MSC therapy was administered in the late phase after kidney transplantation, we found some unexplained adverse events that require further clarification.
To cite this abstract in AMA style:
Večerić-Haler Ž, Sever M, Kojc N, Mlinšek G, Oblak M, Halloran P, Rigler AAleš, Ponikvar JButurović, Arnol M. Autologous Mesenchymal Stem Cells for Treatment of Chronic Antibody-Mediated Kidney Graft Rejection: Report of the First Phase I/II Clinical Case Series [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/autologous-mesenchymal-stem-cells-for-treatment-of-chronic-antibody-mediated-kidney-graft-rejection-report-of-the-first-phase-i-ii-clinical-case-series/. Accessed June 17, 2025.« Back to 2022 American Transplant Congress