Long term follow-up of liver transplant recipients after allogeneic mesenchymal stromal cell infusion

Background: Some properties of mesenchymal stromal cells (MSCs) might
be particularly of interest after organ transplantation. The authors aimed to
report herein the long-term results of their first-in man, prospective, controlled,
phase-1 study evaluating the safety of a single third-party MSC infusion
after liver transplantation (LT).
Methods: Ten liver transplant recipients under standard immunosuppression
received 1.5–3 9 106/kg unrelated third-party MSCs on post-operative
day 3 ! 2 and were prospectively compared to a control group of 10 liver
transplant recipients. Primary endpoints were set to prospectively detect
potential delayed side effects of MSC infusion, and particularly occurrence
of infections and cancers. As secondary endpoints, liver graft- and patient
survivals, graft rejection and function, occurrence of bile duct complications,
and development of anti-HLA antibodies against liver- or MSC-donors were
studied.
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
liver graft- and patient survivals, graft rejection, blood liver tests or occurrence
of bile duct complications. The prevalence of de novo liver DSA
related to HLA-mismatches was two times higher in the MSC group compared
to the control group. Three patients of the MSC group (30%) developed
at least 1 de novo HLA antibody against MSC-donor. All the de novo
class II HLA antibodies against MSC were linked to a shared HLA mismatch
between the liver and MSC donors and 75% of HLA class II shared-mismatches
led to de novo HLA antibodies.
Conclusions: This long-term follow-up confirms the safety of one single
MSC infusion after LT. The potential interesting effects of MSC need to be
confirmed by prospective studies. The development of anti-HLA antibodies
against MSC donor should be further evaluated especially in case of shared
HLAmismatchesbetween graft- and MSC-donors, despite the fact that no
deleterious effect could be detected.