Intraportal induction of mesenchymal stem cells for immunosuppression induction in liver transplantation

Background. Despite the effectiveness of modern immunosuppressive therapy protocols, acute rejection remains a significant challenge in liver transplantation (LT), occurring in up to 40% of cases. One promising strategy to improve graft tolerance and reduce rejection rates is the use of mesenchymal stem cells (MSCs). Administering MSCs directly into the regional circulation of the transplanted liver offers the potential to enhance the effects of standard immunosuppressive therapy by exerting a localized immunosuppressive effect at the graft site. Objective: to evaluate the clinical efficacy of intraportal administration of MSCs during the induction phase of immunosuppressive therapy in patients undergoing LT. Materials and methods. A randomized prospective study was conducted involving two groups of LT recipients. In the experimental group (n = 14), patients received an intraportal infusion of MSCs during transplantation at a dose of 20 × 106 cells. The control group (n = 14) underwent standard transplant reperfusion without MSC administration. The study assessed the safety of the MSC infusion procedure, graft function, incidence and severity of acute rejection, renal function, and tacrolimus levels. Additional assessments included histological and immunohistochemical analyses, as well as fluorescence in situ hybridization (FISH). Results. No complications associated with MSC administration were observed. The MSC group demonstrated faster restoration of graft function, with significantly lower levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by postoperative day 4 (p < 0.05), and normalization of AST achieved by day 10. The incidence of acute rejection was lower in the MSC group (21%) compared to the control group (28%), with only mild to moderate rejection observed in the MSC group. Additionally, expression of matrix metalloproteinase-10 (MMP10) was significantly reduced in the MSC group (p = 0.01). Tacrolimus levels were lower in the MSC group, yet adequate immunosuppression was maintained. This correlated with faster renal function recovery, with serum creatinine levels on day 4 significantly lower in the MSC group compared to controls (80 vs 101 μmol/L, p < 0.05). FISH analysis confirmed the presence of MSCs within the liver graft tissue on postoperative day 7. Conclusion. Intraportal administration of MSCs during LT is a safe approach that enhances faster graft function recovery, reduces the severity of acute rejection, and mitigates tacrolimus-associated nephrotoxicity. These findings support the potential of MSC therapy as a valuable adjunct to standard immunosuppressive regimens in LT.

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