The study reported faster organ regeneration, a lower rate of cellular rejection, and a decreased risk of opportunistic infection in MSC-treated patients. 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. 1. 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]. Therefore, therapeutic strategies, such as rituximab and bortezomib administration, have been used for years to overcome CAMR [2]. Unfortunately, studies including randomized controlled trials have revealed disappointing results [3, 4]. However, many clinicians have identified mesenchymal stem cells (MSCs) as a novel therapy. In previous studies, 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. Although 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. In emerging evidence, the core functions of MSCs as a therapy for many diseases may be regeneration and immunomodulation [6C9]. With Cercosporamide 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. As expected, the application of MSCs in KT is mainly conducted as an alternative to induction agent therapy and minimization of maintenance immunosuppressants [6, 7]. In a pilot study on KT, KTRs with MSC infusion had greater renal function than those without infusion during the five- to seven-year follow-up period [10, 11]. Thereafter, the addition of MSCs to conventional maintenance immunosuppressive agents suggests the possibility of reducing acute rejection after KT [12]. The largest clinical trial to date involved 105 KTRs [13]. The study reported faster organ regeneration, a lower rate of cellular rejection, and a decreased risk of opportunistic infection in MSC-treated patients. In regard to acute rejection, infusion of 2 MSC doses improved rejection as determined by follow-up allograft biopsy [14]. Finally, a study of a rat model reported the possibility of a therapeutic effect of MSCs on chronic allograft nephropathy [15]. On the basis of this rationale, we planned a clinical trial to confirm the safety of MSCs in KTRs with CAMR. In addition, based on previous studies [16, 17], we evaluated changes in T cells to determine the effects of MSCs. 2. Materials and Methods 2.1. Patient Enrollment and Study Protocol This study was a phase 1, single-center, open-label pilot study to confirm safety in patients receiving MSC treatment. The inclusion criteria of the study were patients between 20 and 65 years of Cercosporamide age who had CAMR confirmed by allograft biopsy within 6 months before MSC infusion and were unresponsive to the first-line treatment in our center. The first-line treatment for CAMR in our center was combined therapy with rituximab and intravenous immunoglobulin [18, 19]. In addition, steroid Tlr4 pulse therapy was done with intravenous methylprednisolone 500?mg per day for the first two days, followed by oral prednisolone 30?mg per day. After the first-line treatment, allograft function was assessed with serum creatinine levels and estimated glomerular filtration rate (eGFR) at monthly basis, and unresponsiveness was defined as a patient who failed to show improvement in renal function until 2 months after first-line treatment. Exclusion criteria included patients with hepatitis B, hepatitis C or HIV, a history of cardiovascular disease within 6 months, Cercosporamide a New York Heart Association (NYHA) class 3 or 4 4 condition, a past history of malignancy, pregnancy (if female), and multiorgan transplantation. Finally, two KTRs who were diagnosed with CAMR by allograft.
