Efficacy and Safety of Bone Marrow-Derived Mesenchymal Stem Cells for Chronic Antibody-Mediated Rejection After Kidney Transplantation- A Single-Arm, Two-Dosing-Regimen, Phase I/II Study

作者：Yongcheng Wei, Xiaoyong Chen, Huanxi Zhang, Qun Su, Yanwen Peng, Qian Fu, ­Jun Li­, Yifang Gao, Xirui Li, Shicong Yang, Qianyu Ye, Huiting Huang, Ronghai Deng, Gang Li, Bowen Xu, Chenglin Wu, Jiali Wang, Xiaoran Zhang, Xiaojun Su, Longshan Liu, Andy Peng Xiang, Changxi Wang · 发表于：Frontiers in Immunology · 年份：2021 · DOI：10.3389/fimmu.2021.662441 · 被引用次数：17 · 研究领域：Mesenchymal stem cell research、Renal Transplantation Outcomes and Treatments、Biological Research and Disease Studies

Objective To investigate the efficacy and safety of bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic active antibody-mediated rejection (cABMR) in the kidney allograft. Methods Kidney recipients with biopsy-proven cABMR were treated with allogeneic third-party BM-MSCs in this open-label, single-arm, single-center, two-dosing-regimen phase I/II clinical trial. In Regimen 1 (n=8), BM-MSCs were administered intravenously at a dose of 1.0×10 6 cells/kg monthly for four consecutive months, while in Regimen 2 (n=15), the BM-MSCs dose was 1.0×10 6 cells/kg weekly during four consecutive weeks. The primary endpoints were the absolute change of estimated glomerular filtration rate (eGFR) from baseline (delta eGFR) and the incidence of adverse events associated with BM-MSCs administration 24 months after the treatment. Contemporaneous cABMR patients who did not receive BM-MSCs were retrospectively analyzed as the control group (n =30). Results Twenty-three recipients with cABMR received BM-MSCs. The median delta eGFR of the total BM-MSCs treated patients was -4.3 ml/min per 1.73m 2 (interquartile range, IQR -11.2 to 1.2) 2 years after BM-MSCs treatment (P=0.0233). The median delta maximum donor-specific antibody (maxDSA) was -4310 (IQR -9187 to 1129) at 2 years (P=0.0040). The median delta eGFR of the control group was -12.7 ml/min per 1.73 m 2 (IQR -22.2 to -3.5) 2 years after the diagnosis, which was greater than that of the BM-MSCs treated group (P=0.0342). The incide...