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Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy

1
Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
2
Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy
3
Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7406; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197406
Received: 22 September 2020 / Revised: 2 October 2020 / Accepted: 2 October 2020 / Published: 7 October 2020
(This article belongs to the Special Issue Endothelial Progenitor Cells in Health and Disease)
Cardiovascular disease (CVD) comprises a range of major clinical cardiac and circulatory diseases, which produce immense health and economic burdens worldwide. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable to surgical revascularization. Therefore, more efficient therapeutic approaches are urgently required to promote neovascularization. Therapeutic angiogenesis represents an emerging strategy that aims at reconstructing the damaged vascular network by stimulating local angiogenesis and/or promoting de novo blood vessel formation according to a process known as vasculogenesis. In turn, circulating endothelial colony-forming cells (ECFCs) represent truly endothelial precursors, which display high clonogenic potential and have the documented ability to originate de novo blood vessels in vivo. Therefore, ECFCs are regarded as the most promising cellular candidate to promote therapeutic angiogenesis in patients suffering from CVD. The current briefly summarizes the available information about the origin and characterization of ECFCs and then widely illustrates the preclinical studies that assessed their regenerative efficacy in a variety of ischemic disorders, including acute myocardial infarction, peripheral artery disease, ischemic brain disease, and retinopathy. Then, we describe the most common pharmacological, genetic, and epigenetic strategies employed to enhance the vasoreparative potential of autologous ECFCs by manipulating crucial pro-angiogenic signaling pathways, e.g., extracellular-signal regulated kinase/Akt, phosphoinositide 3-kinase, and Ca2+ signaling. We conclude by discussing the possibility of targeting circulating ECFCs to rescue their dysfunctional phenotype and promote neovascularization in the presence of CVD. View Full-Text
Keywords: cardiovascular disease; ischemic disorders; therapeutic angiogenesis; endothelial colony forming cells; signaling pathways; pharmacological conditioning; genetic modification cardiovascular disease; ischemic disorders; therapeutic angiogenesis; endothelial colony forming cells; signaling pathways; pharmacological conditioning; genetic modification
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MDPI and ACS Style

Faris, P.; Negri, S.; Perna, A.; Rosti, V.; Guerra, G.; Moccia, F. Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy. Int. J. Mol. Sci. 2020, 21, 7406. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197406

AMA Style

Faris P, Negri S, Perna A, Rosti V, Guerra G, Moccia F. Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy. International Journal of Molecular Sciences. 2020; 21(19):7406. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197406

Chicago/Turabian Style

Faris, Pawan, Sharon Negri, Angelica Perna, Vittorio Rosti, Germano Guerra, and Francesco Moccia. 2020. "Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy" International Journal of Molecular Sciences 21, no. 19: 7406. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197406

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