Store-operated Ca2+ entry is expressed in human endothelial progenitor cells

Yuly Sánchez-Hernández, Umberto Laforenza, Elisa Bonetti, Jacopo Fontana, Silvia Dragoni, Marika Russo, José Everardo Avelino-Cruz, Sergio Schinelli, Domenico Testa, Germano Guerra, Vittorio Rosti, Franco Tanzi, Francesco Moccia

Research output: Contribution to journalArticlepeer-review


Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca2+ entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. The present work aimed at investigating SOCE expression in EPCs harvested from both peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both Ca2+ imaging and molecular biology techniques. SOCE was induced upon either pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of the intracellular Ca2+ pool. Further, store-dependent Ca2+ entry was inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2, 3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse transcription-polymerase chain reaction and western blot analyses showed that both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover, pharmacological maneuvers demonstrated that, as well as in differentiated endothelial cells, the signal transduction pathway leading to depletion of the intracellular Ca2+ pool impinged on the phospholipase C/inositol-1,4,5-trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC proliferation. These findings provide the first evidence that EPCs express SOCE, which might thus be regarded as a novel target to enhance the regenerative outcome of cell-based therapy.

Original languageEnglish
Pages (from-to)1967-1981
Number of pages15
JournalStem Cells and Development
Issue number12
Publication statusPublished - Dec 1 2010

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology


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