Anales RANF

S4-04 EMERGING ROLE OF NUCLEOTIDE-METABOLIZING ENZYMES IN REGULATION OF MESENCHYMAL STEM CELLS FATE M. Wujak 1 , K. Roszek 1 1 . Nicolaus Copernicus University, Torun, Poland Extracellular purines, in particular adenosine triphosphate (ATP) and adenosine (Ado), are recognized as the most primitive and widespread chemical messengers. In view of the emerging data, it is evident and widely accepted that an extensive network of diverse nucleotide/nucleoside-metabolizing enzyme activities functions in the extracellular space as an integrated element of the purinergic signaling system (purinome). The concerted action of ecto-enzymes from different classes (hydrolases and transferases) allows for the effective maintenance of nucleotides/nucleosides equilibrium. The ATP-Ado balance is considered as a key regulator of mesenchymal stem cell (MSC) biology, triggering inter alia the differentiation or self ‐ renewal of stem cells. Intensive research efforts from our and other laboratories worldwide indicate that MSC and cells induced to differentiate exhibit different sensitivity to purinergic ligands as well as distinct activity and expression profiles of nucleotide-metabolizing enzymes than mature cells. Our results showed that undifferentiated mesenchymal stem cells present relatively low activity toward ATP and ADP which increases only in the course of differentiation. This is due to the fact that nucleotide signal in the form of ATP is sensed by MSCs as an incentive to their mobilization, increasing the proliferation and migration rates, effectiveness of differentiation and regeneration capacity of a local damage. On the other hand, the differentiated cells increase the expression and activity of ecto-NTPDases, while the ecto-5'-nucleotidase activity decreases. Thus, ATP and ADP hydrolysis becomes the dominant direction of the nucleotides metabolism and serves as a defense mechanism protecting mature cells from cytotoxic nucleotide influence. In this talk, we will consolidate the most important and up ‐ to ‐ date information from the field of ATP- and Ado-mediated regulation of the MSC fate and the emerging role of ecto-enzymes metabolizing nucleotides. This specific hallmark of the MSC purinome should be linked with cell-specific biological potential and capacity for tissue regeneration.