Infusion of Allogeneic Mesenchymal Stromal Cells After Liver Transplantation: A 5-Year Follow-Up

Background Various properties of mesenchymal stromal cells (MSCs) might be particularly of interest after liver transplantation (LT). In this paper, we report the long-term results of their prospective, controlled and first-in-human phase-1 study evaluating the safety of a single MSC infusion after LT. Methods Ten LT recipients under standard immunosuppression received 1.5-3x106 /kg third-party unrelated MSCs on post-operative day 3±2 and were prospectively compared to a control group of 10 LT recipients. Primary endpoints were set to prospectively detect potential delayed side effects of MSC infusion, and particularly occurrence of infections and cancers. Secondary endpoints of liver graft and patient survival, graft rejection and function, occurrence of bile duct complications, and development of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) against liver or MSC donors, were studied. Median follow-up was 85 months. Results There was no difference in overall rates of infection or cancer at 5 years of follow-up between the two groups. There was also no difference in secondary endpoints. The prevalence of de novo liver DSAs related to HLA-mismatches was twice as high in the MSC group compared to the control group. All the de novo class II HLA antibodies against MSCs were linked to a shared HLA mismatch between the liver and MSCs. Conclusions This study confirms the safety of a single MSC infusion after LT. The potential benefits of MSC injections in the context of organ transplantation have still to be demonstrated by larger prospective studies. The development of anti-HLA antibodies against MSC donor should be further evaluated especially in cases of shared HLA mismatches between graft and MSC donors, despite the fact that no deleterious effect has been detected.