EVALUATION OF MESENCHYMAL STEM CELLS SYSTEMIC APPLICATION EFFECT ON LIVER TRANSPLANT FUNCTION RECOVERY IN THE EARLY POSTOPERATIVE PERIOD
Abstract
Background. Liver transplantation is the only radical method of treating of terminal stages of liver failure in cirrhosis. However, despite the progress of surgical techniques and immunosuppression protocols with calcineurin inhibitors application, the incidence of immunological complications is above 40%, which significantly affects the rerecovery of transplant function in the early postoperative period. Objective – to evaluate the effect of systemic of mesenchymal stem cells (MSCs) application on the liver transplant function recovery in the early postoperative period. Material and methods. Randomized prospective study in 30 patients after liver transplantation was performed. The main group (n=15) received systemic MSC therapy, the control group (n=15) – standard immunosuppressive therapy. MSCs were infused intravenously twice: intraoperatively and on the 4th day after surgery at a dose of 2×106 cells per kg. Biochemical parameters of liver function, inflammation markers, results of morphological and immunohistochemical examination of the graft, Tacrolimus concentration, and incidence of complications were assessed. Results. In the MSC group, graft function recoved faster: on the 10th day, the ALT level was 78 versus 98 U/L, bilirubin - 34 versus 53 μmol/L (p<0.05). The frequency of acute cellular rejection was lower in the MSC group (20% versus 33%). Matrix Metalloproteinase-10 (MMP-10) expression in the graft was also lower in the main group (15% versus 20%, p=0.046). MSCs application allowed to maintaining lower concentrations of Tacrolimus (3.1 versus 4.7 ng/ml on the 7th day, p<0.05) without increasing the frequency of rejection. Levels of inflammatory markers were lower in MSCs application: CRP (34 versus 55.5 mg/L) and procalcitonin (0.9 versus 3.79 ng/ml) on the 7th day (p<0.05). There were no complications associated with the administration of MSCs. Conclusion. Systemic application of MSCs is safe and effective method of immunosuppressive therapy after liver transplantation, which accelerates the reсovery of liver transplant function after operation, reduces the risk of acute rejection and allows to minimize the doses of calcineurin inhibitors.
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