Strikingly Different Angiogenic Properties of Endothelial Progenitor Cell Subpopulations: Insights from a Novel Human Angiogenesis Assay

Sieveking, Daniel; Buckle, Andrew; Celermajer, David S.; Ng, M.

doi:10.1016/j.hlc.2008.05.046

Cited by 65 publications

(89 citation statements)

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“…We find that transplantation of EPCs and OECs increases neovascularization of ischemic muscle tissue, consistent with previous reports (32)(33)(34)43), but also find a critical role for sustained delivery of appropriately activated progenitor cells, in place of bolus injections, and a significant benefit of transplanting these two cell populations together. The material system used to deliver vascular progenitors made possible therapeutic angiogenesis, reversal of ischemia, and prevention of necrosis and autoamputation.…”

Section: Discussionsupporting

confidence: 92%

Material-based deployment enhances efficacy of endothelial progenitor cells

Silva

Kim

Kong

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

197

202

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Cell-based therapies are attractive for revascularizing and regenerating tissues and organs, but clinical trials of endothelial progenitor cell transplantation have not resulted in consistent benefit. We propose a different approach in which a material delivery system is used to create a depot of vascular progenitor cells in vivo that exit over time to repopulate the damaged tissue and participate in regeneration of a vascular network. Microenvironmental conditions sufficient to maintain the viability and outward migration of outgrowth endothelial cells (OECs) have been delineated, and a material incorporating these signals improved engraftment of transplanted cells in ischemic murine hindlimb musculature, and increased blood vessel densities from 260 to 670 vessels per mm 2 , compared with direct cell injection. Further, material deployment dramatically improved the efficacy of these cells in salvaging ischemic murine limbs, whereas bolus OEC delivery was ineffective in preventing toe necrosis and foot loss. Finally, material deployment of a combination of OECs with another cell population commonly isolated from peripheral or cord blood, endothelial progenitor cells (EPCs) returned perfusion to normal levels in 40 days, and prevented toe and foot necrosis. Direct injection of an EPC/OEC combination was minimally effective in improving limb perfusion, and untreated limbs underwent autoamputation in 3 days. These results demonstrate that vascular progenitor cell utility is highly dependent on the mode of delivery, and suggest that one can create new vascular beds for a variety of applications with this material-controlled deployment of cells.biomaterial ͉ cell therapy ͉ ischemic diseases ͉ neovascularization ͉ regenerative medicine

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Section: Discussionsupporting

confidence: 92%

Material-based deployment enhances efficacy of endothelial progenitor cells

Silva

Kim

Kong

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

197

202

View full text Add to dashboard Cite

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“…9 -11,15,16 Early EPCs have also been termed "circulating angiogenic cells," and are thought to exert their effects in particular by paracrine mechanisms. 14,17 Furthermore, a relation between the number of in vitro formed colony forming units of early EPCs and endotheliumdependent vasodilation has been suggested. 18 However, it remains unclear whether in vivo endothelial repair capacity of early EPCs is altered in patients with prehypertension or hypertension and is related to an abnormal endotheliumdependent vasodilation and senescence.…”

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confidence: 99%

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

et al. 2010

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Abstract-Prehypertension is a highly frequent condition associated with an increased cardiovascular risk. Endothelial dysfunction is thought to promote the development of hypertension and vascular disease; however, underlying mechanisms remain to be further determined. The present study characterizes for the first time the in vivo endothelial repair capacity of early endothelial progenitor cells (EPCs) in patients with prehypertension/hypertension and examines its relation with endothelial function. Early EPCs were isolated from healthy subjects and newly diagnosed prehypertensive and hypertensive patients (nϭ52). In vivo endothelial repair capacity of EPCs was examined by transplantation into a nude mouse carotid injury model. EPC senescence was determined (RT-PCR of telomere length). NO and superoxide production of EPCs were measured using electron spin resonance spectroscopy analysis. CD34 ϩ /KDR ϩ mononuclear cells and circulating endothelial microparticles were examined by fluorescence-activated cell sorter analysis. Endothelium-dependent and -independent vasodilations were determined by high-resolution ultrasound. In vivo endothelial repair capacity of EPCs was substantially impaired in prehypertensive/hypertensive patients as compared with healthy subjects (re-endothelialized area: 15Ϯ3%/13Ϯ2% versus 28Ϯ3%; PϽ0.05 versus healthy subjects). Senescence of EPCs in prehypertension/hypertension was substantially increased, and NO production was markedly reduced. Moreover, reduced endothelial repair capacity of early EPCs was significantly related to an accelerated senescence of early EPCs and impaired endothelial function. The present study demonstrates for the first time that in vivo endothelial repair capacity of early EPCs is reduced in patients with prehypertension and hypertension, is related to EPC senescence and impaired endothelial function, and likely represents an early event in the development of hypertension. (Hypertension. 2010;55:1389-1397.)

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“…Different types of endothelial progenitor cells have been proposed, in particular "early" and "late" EPCs, based on their appearance in the culture of circulating mononuclear cells in endothelial medium (Hur et al 2004). Early EPCs promote likely endothelial repair (Giannotti et al 2010) and angiogenesis (Sieveking et al 2008) largely by paracrine effects, whereas late EPCs, that are very low in number, may become endothelial cells. The differentiation potential of early EPCs into cardiomyocytes has been questioned (Gruh et al 2006).…”

Section: Adult Stem and Progenitor Cellsmentioning

confidence: 99%

Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy current status and future developments

Templin¹,

Lüscher²,

Landmesser³

2011

Int. J. Dev. Biol.

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Ischemic heart disease is the main cause of death and morbidity in most industrialized countries. Stem-and progenitor cell-based treatment approaches for ischemic heart disease are therefore an important frontier in cardiovascular and regenerative medicine. Experimental studies have shown that bone-marrow-derived stem cells and endothelial progenitor cells can improve cardiac function after myocardial infarction, clinical phase I and II studies were rapidly initiated to translate this concept into the clinical setting. However, as of now the effects of stem/ progenitor cell administration on cardiac function in the clinical setting have not met expectations. Thus, a better understanding of causes of the current limitations of cell-based therapies is urgently required. Importantly, the number and function of endothelial progenitor cells is reduced in patients with cardiovascular risk factors and/or coronary artery disease. These observations may provide opportunities for an optimization of cell-based treatment approaches. This review provides a summary of current evidence for the role and potential of stem and progenitor cells in the pathophysiology and treatment of ischemic heart disease, including the properties, and repair and regenerative capacities of various stem and progenitor cell populations. In addition, we describe modes of stem/progenitor cell delivery, modulation of their homing as well as potential approaches to "prime" stem/progenitor cells for cardiovascular cell-based therapies.

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Strikingly Different Angiogenic Properties of Endothelial Progenitor Cell Subpopulations: Insights from a Novel Human Angiogenesis Assay

Cited by 65 publications

References 0 publications

Material-based deployment enhances efficacy of endothelial progenitor cells

Material-based deployment enhances efficacy of endothelial progenitor cells

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy current status and future developments

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