Abstract
Endothelial progenitor cells (EPCs) have recently been employed in cell-based therapy (CBT) to promote regeneration of ischemic organs, such as heart and limbs. Furthermore, EPCs may sustain tumour vascularisation and provide an additional target for anticancer therapies. CBT is limited by the paucity of cells harvested from peripheral blood and suffers from several pitfalls, including the low rate of engrafted EPCs, whereas classic antiangiogenic treatments manifest a number of side effects and may induce resistance into the patients. CBT will benefit of a better understanding of the signal transduction pathway(s) which drive(s) EPC proliferation, trafficking, and incorporation into injured tissues. At the same time, this information might outline alternative molecular targets to impair tumor neovascularisation and improve the therapeutic outcome of antiangiogenic strategies. An increase in intracellular Ca2+ concentration is the key signal in the regulation of cellular replication, migration, and differentiation. In particular, Ca2+ signalling may regulate cellcycle progression, due to the Ca2+-sensitivity of a number of cycline-dependent kinases, and gene expression, owing to the Ca2+-dependence of several transcription factors. Recent work has outlined the role of the so-called store-operated Ca2+ entry in driving EPC proliferation and migration. Unravelling the mechanisms guiding EPC engraftment into neovessels might supply the biological bases required to improve CBT and anticancer treatments. For example, genetic manipulation of the Ca2+ signalling machinery could provide a novel approach to increase the extent of limb regeneration or preventing tumour vascularisation by EPCs.
Keywords: Endothelial progenitor cells, cell therapy, tumor vascularization, Ca2+ signalling, store operated Ca2+ entry, Orai1, Stim1.
Current Vascular Pharmacology
Title:Ca2+ Signalling in Endothelial Progenitor Cells: A Novel Means to Improve Cell-Based Therapy and Impair Tumour Vascularisation
Volume: 12 Issue: 1
Author(s): Francesco Moccia, Francesco Lodola, Silvia Dragoni, Elisa Bonetti, Cinzia Bottino, Germano Guerra, Umberto Laforenza, Vittorio Rosti and Franco Tanzi
Affiliation:
Keywords: Endothelial progenitor cells, cell therapy, tumor vascularization, Ca2+ signalling, store operated Ca2+ entry, Orai1, Stim1.
Abstract: Endothelial progenitor cells (EPCs) have recently been employed in cell-based therapy (CBT) to promote regeneration of ischemic organs, such as heart and limbs. Furthermore, EPCs may sustain tumour vascularisation and provide an additional target for anticancer therapies. CBT is limited by the paucity of cells harvested from peripheral blood and suffers from several pitfalls, including the low rate of engrafted EPCs, whereas classic antiangiogenic treatments manifest a number of side effects and may induce resistance into the patients. CBT will benefit of a better understanding of the signal transduction pathway(s) which drive(s) EPC proliferation, trafficking, and incorporation into injured tissues. At the same time, this information might outline alternative molecular targets to impair tumor neovascularisation and improve the therapeutic outcome of antiangiogenic strategies. An increase in intracellular Ca2+ concentration is the key signal in the regulation of cellular replication, migration, and differentiation. In particular, Ca2+ signalling may regulate cellcycle progression, due to the Ca2+-sensitivity of a number of cycline-dependent kinases, and gene expression, owing to the Ca2+-dependence of several transcription factors. Recent work has outlined the role of the so-called store-operated Ca2+ entry in driving EPC proliferation and migration. Unravelling the mechanisms guiding EPC engraftment into neovessels might supply the biological bases required to improve CBT and anticancer treatments. For example, genetic manipulation of the Ca2+ signalling machinery could provide a novel approach to increase the extent of limb regeneration or preventing tumour vascularisation by EPCs.
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Moccia Francesco, Lodola Francesco, Dragoni Silvia, Bonetti Elisa, Bottino Cinzia, Guerra Germano, Laforenza Umberto, Rosti Vittorio and Tanzi Franco, Ca2+ Signalling in Endothelial Progenitor Cells: A Novel Means to Improve Cell-Based Therapy and Impair Tumour Vascularisation, Current Vascular Pharmacology 2014; 12 (1) . https://dx.doi.org/10.2174/157016111201140327162858
DOI https://dx.doi.org/10.2174/157016111201140327162858 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
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Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
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