Clinical trial assessing the safety and efficacy of human bone marrow-derived allogeneic mesenchymal stem cell therapy for chronic active antibody-mediated rejection in kidney transplant recipients

Abstract

Background aims: This study evaluated the safety and efficacy of allogenic human bone marrow-derived mesenchymal stem cell (hBM-MSC) therapy in kidney transplant recipients (KTR) with chronic active antibody-mediated rejection (cABMR).

Methods: Seven cABMR patients received four infusions of hBM-MSC (1 × 10⁶ cells/kg), one every other week. The primary outcome was clinical safety, focusing on short-term adverse events. Secondary outcomes included changes in allograft function, mean fluorescence intensity (MFI) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA), allogenic immune response as determined by ELISPOT, lymphocyte subset analysis, infection-free survival, and graft survival compared to 18 historical controls via propensity score matching.

Results: Seven patients received hBM-MSC therapy at a median of 5.4 years (range, 1.6-15.3) after KT and 8.5 months (range, 1.2-20.6) after the diagnosis of cABMR. Six patients completed treatment, and one patient received two doses. No immediate side effects were observed. One patient developed Pneumocystis jirovecii pneumonia (PJP) 3 weeks after treatment and died 6 weeks post-treatment. Among those who completed therapy, the eGFR slope shifted from -Δ16.6% to -Δ2.4% over the 6 month periods before and after treatment, suggesting a stabilization of eGFR decline, proteinuria decreased, and MFI of HLA-DSA declined. T-cell subset analysis showed increased CD8+CD45RA+CCR7- T cells and CD4+CD25+CD127low T cells with decreased CD8+CCR7+CD45RO+/CD45RA+ T cells. Kaplan-Meier analysis demonstrated no significant difference in infection-free survival or death-censored graft survival compared to those of the propensity score-matched control group. No significant difference in infection-free survival or death-censored graft survival compared to those of the propensity score-matched control group.

Conclusions: hBM-MSC therapy was generally well tolerated for KTR with cABMR and demonstrated favorable immunomodulatory effects. Larger, controlled trials with extended period are required to validate these findings and better define the role of hBM-MSC therapy for cABMR.

Keywords: chronic antibody-mediated rejection; clinical outcomes; immunomodulation; kidney transplantation; mesenchymal stem cells.