A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long-term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord-derived mesenchymal stem cell (UC-MSC) therapy in liver transplant patients with acute graft rejection. Twenty-seven liver allograft recipients with acute rejection were randomly assigned into the UC-MSC infusion group or the control group. Thirteen patients received one infusion of UC-MSCs (1 x 10(6)/kg body weight); one patient received multiple UC-MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow-up for 12 weeks after UC-MSC infusions. No side effects occurred in treated patients. Four weeks after UC-MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12-week follow-up period. Importantly, allograft histology was improved after administration of UC-MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC-MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC-MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect.