Endothelial progenitor cells (EPCs) have recently been employed in cell-based therapy (CBT) to promote neovascularization
and regeneration of ischemic organs, such as heart and limbs. Furthermore, EPCs may be recruited from bone marrow by growing tumors
to drive the angiogenic switch through physical engrafting into the lumen of nascent vessels or paracrine release of pro-angiogenic factors.
CBT is hampered by the paucity of EPCs harvested from peripheral blood and suffered from several pitfalls, including the differentiation
outcome of transplanted cells and low percentage of engrafted cells. Therefore, CBT will benefit from a better understanding of
the signal transduction pathway(s) which govern(s) EPC homing, proliferation and incorporation into injured tissues. At the same time,
this information might outline alternative molecular targets to combat tumoral neovascularization. We have recently found that storeoperated
Ca2+ entry, a Ca2+-permeable membrane pathway that is activated upon depletion of the inositol-1,4,5-trisphosphate-sensitive
Ca2+ pool, is recruited by vascular endothelial growth factor to support proliferation and tubulogenesis in human circulating endothelial
colony forming cells (ECFCs). ECFCs are a subgroup of EPCs that circulate in the peripheral blood of adult individuals and are able to
proliferate and differentiate into endothelial cells and form capillary networks in vitro and contribute to neovessel formation in vivo. The
present review will discuss the relevance of SOCE to ECFC-based cell therapy and will address the pharmacological inhibition of storedependent
Ca2+ channels as a promising target for anti-angiogenic treatments.
Keywords: Endothelial progrenitor cells, store-operated calcium entry, calcium signalling, neovascularisation, cardiovascular diseases, cellbased
therapy, tumour, antiangiogenic drugs, Stim1, Orai1
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