MSC in clinics: Liver Transplantation
organ transplantation | : Surgery [Human health sciences] | : Chirurgie [Sciences de la santé humaine]
For several years, mesenchymal stem cells (MSC) have been evaluated in vivo and in vitro for their immunomodulatory, anti-inflammatory, anti- ischemia-reperfusion injury and “tissue repair” properties. These characteristics could make them interesting in various clinical applications, and particularly in organ transplantation. Taking advantage of our centre expertise and experience concerning MSC use in graft-versus-host disease after bone marrow transplantation and using already functioning GMP-compliant laboratory able to produce clinical-grade MSC, we initiated in 2011 a first trial exploring safety and tolerability of third party MSC infusions after kidney or liver transplantation in a prospective phase I-II study. In this study, after successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppressive treatment (tacrolimus, mycophenolate, steroids) receive an intravenous infusion of 1.5 - 3x106/kg of third-party MSC, on post-operative day 3+/-2. These patients are prospectively compared to the same number of liver and kidney transplant recipients who meet inclusion criteria but do not receive MSC infusion. Safety is assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential is evaluated by rejection episode rates, graft/patient survivals, immunohistology of 3-month (kidney) and 6-month (liver) graft biopsies, and in vitro evaluation of recipient immunity profile. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression is attempted in recipients who received MSC. Inclusion of liver patients is now complete, and to date 3 kidney patients received MSC. Primary results will be presented, and complete 6-month liver results are expected for the end of 2014. The next step will be to assert the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials.