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Mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contains multipotent stem cells capable of originating a variety of mesenchymal cell lineages. Here we studied MSCs from the human adipose tissue and examined Ca2+ signaling initiated by a variety of GPCR ligands, focusing largely on adrenergic and purinergic agonists. Although all tested compounds were capable of mobilizing intracellular Ca2+ in MSCs, cell responsiveness to a particular agonist varied from cell to cell. Characteristic of agonist responses was that they were generated in an “all-or-nothing” fashion: at low concentrations agonists never elicited small or intermediate responses but initiated large and quite similar Ca2+ transients at all concentrations above the threshold. The inhibitory analysis and Ca2+/IP3 uncaging pointed at the phosphoinositide cascade as a pivotal pathway responsible for agonist transduction and implicated Ca2+-induced Ca2+ release (CICR) mediated by IP3 receptors in shaping agonists-dependent Ca2+ signals. Altogether, our data suggest that agonist transduction in MSCs includes two fundamentally different stages: an agonist initially triggers a local, gradual, and relatively small Ca2+ signal, which next stimulates CICR to accomplish transduction with a large and global Ca2+ transient, thereby generating invariant cellular response irrespective of agonist concentration.

Calcium Signaling Initiated by Agonists in Mesenchymal Stromal Cells from the Human Adipose Tissue