Clinical Trial of Allogeneic Mesenchymal Stem Cell Therapy for Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients Unresponsive to Rituximab and Intravenous Immunoglobulin

Tae Hyun Ban,Hyung Duk Kim,Bo-Mi Kim,Eun Jeong Ko,Byung Ha Chung,Chul Woo Yang,Sua Lee,Kyoung-Woon Kim,Alessandro Faroni

doi:10.1155/2021/6672644

Abstract

Clinical trials of biologic agents for chronic active antibody-mediated rejection (CAMR) in kidney transplant recipients (KTRs) have been disappointing. We performed a clinical trial of mesenchymal stem cell (MSC) treatment in KTRs with CAMR unresponsive to rituximab and intravenous immunoglobulin. This study was a phase 1 clinical trial to confirm patient safety. Two patients with CAMR unresponsive to rituximab and intravenous immunoglobulin were included. Each patient received allogeneic MSCs for 4 cycles (1 × 106 cells/kg every other week) via the peripheral vein in the distal arm. We observed adverse events and renal function for 6 months after the final MSC infusion and analyzed changes in immunomodulatory parameters in the peripheral blood between the start of treatment and 3 months after the final MSC infusion. There were no serious adverse events during the study period. Renal function was stable during MSC treatment but gradually decreased between the final MSC infusion and the study endpoint (patient 1: creatinine levels ranged from 3.01 mg/dL to 7.81 mg/dL, patient 2: 2.87 mg/dL to 3.91 mg/dL). In peripheral blood sample analysis between the start of treatment and 3 months after the final MSC infusion, there were similar trends for immunomodulatory markers. Our study showed that there were no serious adverse events for six months after allogeneic MSC treatment in KTRs with CAMR refractory to rituximab and intravenous immunoglobulin, but further studies need to define the efficacy of MSC treatment in CAMR.

Highlights

Chronic active antibody-mediated rejection (CAMR) in kidney transplant recipients (KTRs) is a major cause of late kidney allograft loss
CAMR in the patients was diagnosed with allograft biopsy owing to increased serum creatinine levels at 6 months in patient #1 and at 2 months in patient #2 before mesenchymal stem cell (MSC) treatment
Renal function was stable through the final MSC infusion

Summary

Introduction

Chronic active antibody-mediated rejection (CAMR) in kidney transplant recipients (KTRs) is a major cause of late kidney allograft loss. CAMR-related allograft failure recently occurred in nearly half of KTRs [1]. Therapeutic strategies, such as rituximab and bortezomib administration, have been used for years to overcome CAMR [2]. MSC treatment was shown to be effective in various kidney diseases [5]. These effects may originate from the potential of MSCs to differentiate into diverse cell types, including osteoblasts, chondrocytes, adipocytes, endothelial cells, and other organ cells. MSC therapy is expected to be a novel promising treatment for CAMR in kidney transplantation (KT), the therapeutic mechanism of MSCs is not fully understood. With regards to the therapeutic mechanisms of MSCs, their effects on KTRs are expected to produce favorable outcomes, such as minimization or withdrawal of immunosuppressive agents, decreased infectious complications, and reduced incidence of rejection

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