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

Abstract

Mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contain multipotent stem cells capable of originating a variety of mesenchymal cell lineages. By using Ca2+ imaging and the Ca2+ dye Fluo-4, we studied MSCs from the human adipose tissue and examined Ca2+ signaling initiated by a variety of GPCR ligands, focusing primarily on adrenergic and purinergic agonists. Being characterized by a relative change of Fluo-4 fluorescence, agonist-induced Ca2+ responses were generated in an “all-or-nothing” fashion. Specifically, at relatively low doses, agonists elicited undetectable responses but initiated 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) 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. By involving the trigger-like mechanism CICR, a cell is capable of generating Ca2+ responses of virtually universal shape and magnitude at different agonist concentrations above the threshold