Endothelial progenitor cells (EPCs) are a sub-population of bone marrow-derived mononuclear cells that are released in circulation to restore damaged endothelium during its physiological turnover or rescue blood perfusion after an ischemic insult. Additionally, they may be mobilized from perivascular niches located within larger arteriesâ wall in response to hypoxic conditions. For this reason, EPCs have been regarded as an effective tool to promote revascularization and functional recovery of ischemic hearts, but clinical application failed to exploit the full potential of patients-derived cells. Indeed, the frequency and biological activity of EPCs are compromised in aging individuals or in subjects suffering from severe cardiovascular risk factors. Rejuvenating the reparative phenotype of autologous EPCs through a gene transfer approach has, therefore, been put forward as an alternative approach to enhance their therapeutic potential in cardiovascular patients. An increase in intracellular Ca2+concentration constitutes a pivotal signal for the activation of the so-called endothelial colony forming cells (ECFCs), the only known truly endothelial EPC subset. Studies from our group showed that the Ca2+toolkit differs between peripheral blood- and umbilical cord blood (UCB)-derived ECFCs. In the present article, we first discuss how VEGF uses repetitive Ca2+spikes to regulate angiogenesis in ECFCs and outline how VEGF-induced intracellular Ca2+oscillations differ between the two ECFC subtypes. We then hypothesize about the possibility to rejuvenate the biological activity of autologous ECFCs by transfecting the cell with the Ca2+-permeable channel Transient Receptor Potential Canonical 3, which selectively drives the Ca2+response to VEGF in UCB-derived ECFCs.
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/jcp.26152|
|Codice identificativo ISI:||WOS:000424644700018|
|Codice identificativo Scopus:||2-s2.0-85041852455|
|Titolo:||TRPC3-mediated Ca2+signals as a promising strategy to boost therapeutic angiogenesis in failing hearts: The role of autologous endothelial colony forming cells|
|Appare nelle tipologie:||1.1 Articolo in rivista|