CD133+ adult bone marrow stem cells to promote liver regeneration - the role of platelets for hepatic homing and analyses of released factors for differentiation as well as proliferation subsequent to clinical hepatic resection

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Initial clinical experience with a novel concept to promote liver regeneration in 8 patients, scheduled for extended right liver resection, demonstrated a 2.5-fold increase of proliferation rates of left liver lobe segments subsequent to application of CD133+ bone marrow stem cells (BMSC) in addition to portal venous embolization of the right liver lobe. To gain insight in faith and mechanisms of CD133+BMSC applied to improve physiological liver regeneration processes 2D-cell co-culture models of CD133+BMSC with either primary liver cells or isolated sinusoidal endothelial cells (SEC) and 2 whole liver perfusion models will be utilized. In concert with a xenogeneic pre-clinical small animal model - analogue to our clinical concept – as well as clinical experimental studies, the potential of platelets and platelet derived microparticles (PMP) to promote CD133+BMSC participation in liver regeneration with consequent therapeutic options will be explored. In patients subsequent to liver resection, cytokines, growth factors and levels of platelet activation will be correlated with peripheral CD133+ cell mobilisation, levels of hepatic parenchymal loss and liver function and investigated for their capacity to modulate differentiation/ proliferation of CD133+BMSC in co-culture with primary liver cells. These studies will help to understand and improve a therapeutic concept using CD133+BMSC to promote liver regeneration. Beyond the surgical treatment of oncological patients with an indication for extensive partial hepatectomy the findings derived from these studies may have an impact on therapeutic promotion of organ regeneration following other scenarios of acute and chronic liver damage.