Z Gastroenterol 2011; 49 - P3_10
DOI: 10.1055/s-0030-1269625

Role of exo- and endogeneous mesenchymal stem cells in liver ischemia reperfusion injury

E Eggenhofer 1, V Benseler 2, P Renner 1, FC Popp 1, E Geissler 1, HJ Schlitt 3, MH Dahlke 2
  • 1Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg
  • 2Klinik und Poliklinik für Chirurgie der Universität Regensburg, Regensburg
  • 3Department of Surgery, University of Regensburg, Regensburg

Introduction: Mesenchymal stem cells (MSC) are one of the most promising cell populations for cell based immune therapy in solid organ transplantation. A transplanted organ is up against immune response of the recipient but also stress and tissue damage caused by ischemia and reperfusion. Besides their immuno suppressive function, MSC exert also beneficial influence on tissue regeneration.

Methods: Influence of MSC were investigated in a murine heterotopic heart tranplantation model and a ischemia/reperfusion injury (IRI) liver damage model. We used two different types of MSC. On the one hand exogenous MSC, isolated and cultivated from murine bone marrow, on the other hand endogenous MSC, mobilized from recipients bone marrow into peripheral blood. Mobilization was done by daily application of VEGF for four days followed by nonrecurring application of Plerixafor®.

Results: Therapy by exogenous MSC prolonged survival of allograft significantly (median graft survival 40 days vs. 9 days). On the other hand without concurrent immunosuppression we saw (at least with donor-type MSC) sensibilization of the recipient and therefore accelerated allograft rejection (median graft survival 7 days). For this reason we investigated the effect of autologous exo- and endogeneous MSC in a transplantation related IRI liver damage model. Application of the mobilization protocol for endogenous MSC resulted in effective increase of MSC frequency in peripheral blood of the recipients (8 times more), which is a first, very promising partial success concerning the cell-therapy with endogenous MSC.

Discussion: A potential clinical application of ex vivo generated endogenous MSC is associated with severe problems, eg. sensibilization of the recipient, contamination or tumorigenic potential. Therefore, achieving immune protection and organ regeneration by mobilization of recipients own MSC is a very promising approach for prospective clinical usage.

liver damage - liver transplantation - stem cells