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

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Mechanisms underlying the process of homing and sequestration of CD133+ progenitor cells after liver injury and their differentiation remain unclear. Given the requirement of ectonucleotidases for vascular reconstitution during liver regeneration, we have examined within the first year whether CD133+/CD45+ BMSCs functions are dictated by purinergic ectoenzymes. We could show that CD39/NTPDase1 (and CD39L1/NTPDase2) are expressed by CD133+/CD45+ BMSCs and that purinergic signaling plays crucial roles in mobilization and function of these cells in boosting liver regeneration. Based on these observations, we plan to investigate in the second year whether and how ADP-associated platelet activation, initiated by CD39L1/NTPDase2, facilitates CD133+/CD45+ stem cell mediated liver regeneration. We will investigate liver regeneration in wild-type, CD39L1/NTPDase2 null and CD39/NTPDase1 null mice with induced thrombocytopenia or thrombocytosis following 70% hepatectomy. We plan to administer i.v. CD133+/CD45+ BMSCs from wild-type and named knock-out mice to further address the importance of local expression of ectonucleotidases.