Minimization of immunosuppressive therapy using mesenchymal stem cells in liver transplantation in patients with renal injury

The aim of the study was to evaluate the possibility of using mesenchymal stem cells (MSCs) to minimize  the nephrotoxic effects of tacrolimus in liver transplant recipients with high risk of developing of acute kidney injury.

In a randomized prospective study, 60 patients who had undergone liver transplantation participated: 30 patients received combined MSC therapy (local intraportal and systemic intravenous administration), 30 patients received standard immunosuppressive therapy. In the MSC group, a faster recovery of graft function with an accelerated decrease in ALT  on days 7 and 10 (p < 0.05) was established with a significantly lower tacrolimus concentration at all follow-up periods  (on day 14: 4.8 (2.4; 5.7) ng/ml compared to 6.3 (4.2; 8.8) ng/ml in the control group, p = 0.005). The frequency of immuno- logical graft dysfunction was 20% in both groups. However, in the MSC group exhibited a lower rejection activity index  (RAI 6 (4; 7) versus 7 (4; 8) points) and no cases of humoral rejection. Analysis of the immunophenotype revealed  the formation of an “immunosuppressive window” by the 4th day of the postoperative period in the MSC group, characterized by a decrease in the absolute number of CD16+56+ natural killer cells and CD3+CD4+ effector memory T-cells with  an increase in the level of dendritic cells and immunosuppressive B1a-lymphocytes. The minimization of tacrolimus contributed to faster recovery of renal function with lower creatinine levels (p < 0.05) and higher GFR values (p < 0.05). The duration  of stay in the intensive care unit and the total duration of hospitalization in the MSC group were shorter.

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