Outgrowth Endothelial Cells: Characterization and Their Potential for Reversing Ischemic Retinopathy

Medina, Reinhold J.; O'Neill, Christina; Humphreys, Mervyn; Gardiner, Tom; Stitt, Alan W.

doi:10.1167/iovs.09-4951

Cited by 152 publications

(152 citation statements)

References 37 publications

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“…Evidence for this in ECFC biology comes from the relatively low number of cells that engraft at the ischemic site, which nonetheless can provide a substantial therapeutic benefit (6,8). Furthermore, it is rare to find vessels that consist of injected cells only.…”

Section: Discussionmentioning

confidence: 99%

“…ECFCs can be isolated from human cord or peripheral blood and have robust clonal proliferative potential. They have been reported to home to the site of tissue ischemia after intravenous injection, where they improve circulation in a model of myocardial infarction (4), stroke (5), ischemic retinopathy (6,7), and ischemic limb injury (8,9). Although a paracrine trophic rescue effect of ECFCs has been postulated (10,11), factors that may mediate this effect remain poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

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CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

et al. 2017

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“…Recently we have characterized two EPC subtypes in vitro: early EPCs (herein called myeloid angiogenic cells [MACs]) and outgrowth endothelial cells (OECs) (11) (also known as endothelial colony-forming cells). OECs possess well-defined endothelial progenitor characteristics such as commitment to an endothelial lineage, de novo tubulogenic potential and an ability to fully incorporate into a resident vascular network (12). In contrast, MACs show none of these EPC properties; however, MACs may still play a significant role in therapeutic angiogenesis (13,14).…”

Section: Introductionmentioning

confidence: 99%

Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8

Medina

O'Neill

O’Doherty

et al. 2011

Mol Med

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162

141

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Endothelial progenitor cells (EPCs) promote angiogenesis, and clinical trials have shown such cell therapy to be feasible for treating ischemic disease. However, clinical outcomes have been contradictory owing to the diverse range of EPC types used. We recently characterized two EPC subtypes, and identified outgrowth endothelial cells as the only EPC type with true progenitor and endothelial characteristics. By contrast, myeloid angiogenic cells (MACs) were shown to be monocytic cells without endothelial characteristics despite being widely described as "EPCs." In the current study we demonstrated that although MACs do not become endothelial cells or directly incorporate into a microvascular network, they can significantly induce endothelial tube formation in vitro and vascular repair in vivo. MAC-derived interleukin-8 (IL-8) was identified as a key paracrine factor, and blockade of IL-8 but not vascular endothelial growth factor (VEGF) prevented MAC-induced angiogenesis. Extracellular IL-8 transactivates VEGFR2 and induces phosphorylation of extracellular signal-regulated kinases. Further transcriptomic and immunophenotypic analysis indicates that MACs represent alternative activated M2 macrophages. Our findings demonstrate an unequivocal role for MACs in angiogenesis, which is linked to paracrine release of cytokines such as IL-8. We also show, for the first time, the true identity of these cells as alternative M2 macrophages with proangiogenic, antiinflammatory and pro-tissue-repair properties.

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“…Human umbilical cord blood is enriched with ECFCs and the concentration of these circulating cells declines with aging or disease 10 . Recent studies suggest that ECFC may play important roles in vascular repair or regeneration in situations of vascular injury, myocardial infarction, or retinopathy [17][18][19] . Here, we have described simple and efficient methodologies for the derivation, cloning, expansion, and in vitro as well as in vivo characterization of ECFCs from human umbilical CB.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Functional Characterization of Endothelial Colony Forming Cells Derived from Human Umbilical Cord Blood

Prasain

Meador

Yoder

2012

JoVE

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Longstanding views of new blood vessel formation via angiogenesis, vasculogenesis, and arteriogenesis have been recently reviewed 1 . The presence of circulating endothelial progenitor cells (EPCs) were first identified in adult human peripheral blood by Asahara et al. in 1997 2 bringing an infusion of new hypotheses and strategies for vascular regeneration and repair. EPCs are rare but normal components of circulating blood that home to sites of blood vessel formation or vascular remodeling, and facilitate either postnatal vasculogenesis, angiogenesis, or arteriogenesis largely via paracrine stimulation of existing vessel wall derived cells . No specific marker to identify an EPC has been identified, and at present the state of the field is to understand that numerous cell types including proangiogenic hematopoietic stem and progenitor cells, circulating angiogenic cells, Tie2 + monocytes, myeloid progenitor cells, tumor associated macrophages, and M2 activated macrophages participate in stimulating the angiogenic process in a variety of preclinical animal model systems and in human subjects in numerous disease states 4,5 . Endothelial colony forming cells (ECFCs) are rare circulating viable endothelial cells characterized by robust clonal proliferative potential, secondary and tertiary colony forming ability upon replating, and ability to form intrinsic in vivo vessels upon transplantation into immunodeficient mice [6][7][8] . While ECFCs have been successfully isolated from the peripheral blood of healthy adult subjects, umbilical cord blood (CB) of healthy newborn infants, and vessel wall of numerous human arterial and venous vessels [6][7][8][9]

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Outgrowth Endothelial Cells: Characterization and Their Potential for Reversing Ischemic Retinopathy

Abstract: As a distinct EPC population, OECs have potential as therapeutic cells to vascularize the ischemic retina.

Cited by 152 publications

References 37 publications

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8

Phenotypic and Functional Characterization of Endothelial Colony Forming Cells Derived from Human Umbilical Cord Blood

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