Project Details
Projekt Print View

Platelet activation triggered by CD39L1/NTPDase2 facilitates CD133+/CD45* stem cell mediated liver generation

Subject Area General and Visceral Surgery
Term from 2009 to 2011
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 144017391
 
Final Report Year 2011

Final Report Abstract

Dr. Moritz Schmelzle joined the Prof. Simon C. Robson laboratory at the Transplant Institute, Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA, as a DFG Postdoctoral Research Fellow in 2009. Based on experiences at the Department of Surgery, University Hospital Düsseldorf with therapeutical administration of CD133+ bone marrow-derived hematopoietic stem cells (HSC), he planned to focus on mechanisms possibly involved in mobilization and functions of CD133+ HSC in liver regeneration. In Boston, Dr. Moritz Schmelzle investigated the role of purinergic signaling in HSC- mediated liver regeneration after liver surgery. Effects of regulated hydrolysis of extracellular adenosine triphosphate (ATP) to adenosine by CD39 on HSC responses were studied in vitro and in vivo using wild type and mice null for Cd39 and Cd39L1. Translational aspects were strengthened in clinical studies, which were performed in an ongoing collaboration with the Department of Surgery, University Hospital Düsseldorf. Dr. Moritz Schmelzle has identified distinct CD133+ HSC subsets expressing the plasma membrane ectonucleotidase CD39. Dramatic differences for the mobilization potential of CD39high and CD39low CD133+ HSC were noted after liver injury, with CD39high CD133+ HSC subsets being preferentially mobilized. Migration of CD133+ HSC towards vascular endothelial growth factor (VEGF) was shown to be, at least in part, dependent on the hydrolysis of extracellular ATP by CD39 and adenosine binding to adenosine-type purinergic 1 receptors (P1R) A2A. Additional studies in humans provided clinical significance by showing that CD133+ HSC are mobilized after liver resection, with CD39 positive subsets being at significantly higher levels. Dr. Moritz Schmelzle has further shown that CD133+ HSC boost liver regeneration by modulating vascular inflammation and coordinating endothelial cell and hepatocyte proliferation following partial hepatectomy. Based on studies in vitro and in vivo, Dr. Moritz Schmelzle proposed mechanisms by which CD39high CD133+ BMSCs scavenge high levels of extracellular ATP at sites of injury and in turn decrease IL-1ß levels in LSEC.

 
 

Additional Information

Textvergrößerung und Kontrastanpassung