The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic

O'Leary, Olivia; Canning, Paul; Reid, Emma; Bertelli, Pietro Maria; McKeown, Stuart; Brines, Michael; Cerami, Anthony; Du, Xuan; Xu, Heping; Chen, Mei; Dutton, Louise; Brazil, Derek P.; Medina, Reinhold J.; Stitt, Alan W.

doi:10.1016/j.exer.2019.03.001

Cited by 19 publications

(18 citation statements)

References 60 publications

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“…The reparative outcome of ECFC transplantation was also enhanced by alleviating the pro-inflammatory milieu typical of the ischemic retina. The systemic delivery of ARA290 (cibinetide), a peptide-based on the Helix-B domain of erythropoietin (EPO), exerted a local anti-inflammatory effect in a murine model of oxygen-induced retinopathy (OIR), thereby boosting ECFCs-induced neovascularization [ 78 ]. In addition to integrating within emerging neovessels, ECFCs can support retinal neovascularization in a paracrine manner.…”

Section: Endothelial Colony-forming Cells: Origin Mechanisms Of Amentioning

confidence: 99%

“…Consistently, a human platelet lysate gel has been recently designed to provide a 2D matrix enriched with growth factors and able to promote ECFC amplification and networking formation [ 141 ]. Likewise, ex vivo proliferation is enhanced by pre-conditioning ECFCs with the pro-angiogenic cues fucoidan [ 142 , 143 , 144 ] and SDF-1α [ 145 , 146 ], with the hexapeptide SFLLRN, which mimics the thrombin effect on PAR-1 [ 53 , 147 , 148 ], with the erythroid growth factor EPO [ 78 , 106 , 149 , 150 , 151 , 152 ], with the isoflavone genistein [ 153 , 154 ], with nicotine [ 155 ], and with an acidic growth medium [ 129 , 156 ]. Hypoxic pre-conditioning has also been proposed as an alternative approach to accelerate the ex vivo expansion of primary ECFCs [ 157 , 158 ], although subsequent studies demonstrated that their angiogenic activity is compromised under hypoxia [ 131 , 132 ].…”

Section: Manipulation Of Pro-angiogenic Signaling Pathways To Imprmentioning

confidence: 99%

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

Faris

Negri

Perna

et al. 2020

IJMS

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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.

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Section: Endothelial Colony-forming Cells: Origin Mechanisms Of Amentioning

confidence: 99%

Section: Manipulation Of Pro-angiogenic Signaling Pathways To Imprmentioning

confidence: 99%

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

Faris

Negri

Perna

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The reparative outcome of ECFC transplantation was also enhanced by diminishing the pro-inflammatory milieu typical of the ischemic retina. Systemic delivery of ARA290 (cibinetide), a peptide-based on the Helix-B domain of erythropoietin (EPO), exerted a local anti-inflammatory effect in a murine model of oxygen-induced retinopathy (OIR), thereby boosting ECFCs-induced neovascularization [79]. Besides integrating within emerging neovessels, ECFCs can support retinal neovascularization in a paracrine manner.…”

Section: 22mentioning

confidence: 99%

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

Faris

Negri

Perna

et al. 2020

Preprint

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Cardiovascular disease (CVD) comprises a group of heart and circulatory disorders, which are regarded as a global medical issue with high prevalence and mortality rates. 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. Circulating endothelial colony forming cells (ECFCs), in turn, represent truly endothelial precursors able to aggregate into bidimensional tube networks and to originate patent vessels. Accordingly, ECFCs provide the most rationale and promising cellular candidate for therapeutic purposes. The current review provides a brief outline on the origin and characterization of ECFCs and a summary of the progress in preclinical studies aiming at assessing their efficacy in a variety of ischemic disorders, including AMI, PAD, ischemic brain disease and retinopathy. We also describe how to enhance the vasoreparative potential of ECFCs by boosting specific pro-angiogenic signalling pathways either pharmacologically or through gene manipulation. Taken together, these observations suggest that ECFCs represent a useful strategy to treat ischemic diseases.

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“…Recent research in China and elsewhere has examined the non-hematopoietic aspects of EPO (14)(15)(16). There is now evidence that EPO is a multifunctional cytokine (17). Thus, in addition to regulating erythropoiesis (which increases tissue oxygen supply) EPO also has anti-apoptosis, anti-inflammatory, antioxidant, angiogenesis, cell proliferation, and anti-tumor effects (18).…”

Section: Introductionmentioning

confidence: 99%

Advances in Understanding the Effects of Erythropoietin on Renal Fibrosis

et al. 2020

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Renal fibrosis is the common manifestation of the pathogenesis of end-stage renal disease that results from different types of renal insult, and is a hallmark of chronic kidney disease (CKD). The main pathologic characteristics of renal fibrosis are renal interstitial fibroblast hyperplasia and the aberrant and excessive deposition of extracellular matrix, pathologies that lead to the destruction of normal renal tubules and interstitial structures. However, the biological significance of fibrosis during the progression of CKD is not clear, and there are no approved clinical treatments for delaying or reversing renal fibrosis. Studies of the mechanism of renal fibrosis and of potential measures of prevention and treatment have focused on erythropoietin (EPO), a hormone best known as a regulator of red blood cell production. These recent studies have found that EPO may also provide efficient protection against renal fibrosis. Future therapeutic approaches using EPO offer new hope for patients with CKD. The aim of the present review is to briefly discuss the role of EPO in renal fibrosis, to identify its possible mechanisms in preventing renal fibrosis, and to provide novel ideas for the use of EPO in future treatments of renal fibrosis.

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The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic

Cited by 19 publications

References 60 publications

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

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

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

Advances in Understanding the Effects of Erythropoietin on Renal Fibrosis

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