Mesenchymal stem cells in liver transplantation: аssessment of long-term results

Introduction . Transplantation is an effective method of treating patients with end stage liver diseases. Long-term results are determined by two main factors: the development of immunological complications and calcineurin inhibitor nephrotoxity. Application of mesenchymal stem cells (MSCs), which modulate the immune response, is a promising effective method to optimize the treatment results in patients after liver transplantation. The objective of the study was to evaluate the long-term results of mesenchymal stem cells application in liver transplantation. Material and methods . A retrospective study was performed, which included 186 patients after liver transplantation (2015–2023). The MSC group (n=93) received MSCs according to four protocols: local, systemic, combined administration, therapy for acute kidney injury; the control group (n=93) received the standard treatment. The median follow-up was 3 (2;5) years, the follow-up period being from 1-8 years. The patient survival, graft and renal function, depth of immunosuppressive therapy, anti-HLA antibody levels, and lymphocyte immunophenotype were assessed. Results . In the MSC group the incidence of immunological dysfunction of the liver allograft was decreased (22% versus 40%, p<0.05), the development of stage 3 chronic kidney disease (23.4% versus 68.2%, p<0.05) and formation of anti-HLA antibodies (5% versus 20%, p<0.05) were reduced. The use of MSCs made it possible to reduce the Tacrolimus doses (4.15 vs. 5.2 ng/mL, p=0.001) without increasing the risk of rejection. Eight-year survival in MSC group was 87.7% versus 82.9% in the control group. Specific to immunological tolerance changes in the immunophenotype were identified. Conclusion . Using MSCs in liver transplantation improves long-term outcomes by reducing the incidence of immunological complications, preserves the renal function, and reduces the need for high-dose immunosuppression.