Isolation of endothelial cells and their progenitor cells from human peripheral blood

Boyer, Michael W.; Townsend, Laurace E.; Vogel, L.; Falk, Jeffrey; Reitz-Vick, D; Trevor, Katrina T.; Villalba, Maribel; Bendick, Phillip J.; Glover, John L.

doi:10.1016/s0741-5214(00)70080-2

Cited by 149 publications

(81 citation statements)

References 26 publications

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“…106 Heterologous, homologous, or autologous EPCs administered systemically to animals with operatively induced hindlimb ischemia were found to incorporate themselves into foci of neovascularization in ischemic muscles of the affected hindlimb. These findings, together with those of other recent studies, [107][108][109][110] have been interpreted as evidence of postnatal "vasculogenesis." 101,105 …”

Section: Postnatal Vasculogenesissupporting

confidence: 82%

Estrogen and Angiogenesis

Losordo

Isner

2001

ATVB

304

194

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Abstract-Multiple lines of evidence suggest that estrogen directly modulates angiogenesis via effects on endothelial cells.Under physiological conditions, angiogenesis is routinely observed in the uterus in association with fluctuations in the levels of circulating estradiol and other sex steroids. In pathological circumstances, such as breast cancer, a clear association between estrogen, estrogen receptor expression by endothelial cells, angiogenic activity, and/or tumor invasiveness has been made. Studies performed in our laboratory have revealed that estradiol accelerates functional endothelial recovery after arterial injury. Despite these consistent observations, the mechanisms by which estrogen regulates angiogenesis under physiological and pathological circumstances have not been defined. Key Words: estrogen Ⅲ angiogenesis Ⅲ vasculogenesis Ⅲ endothelium Ⅲ endothelial progenitor cells I n adult organisms, angiogenesis is virtually absent under normal conditions, except in the female reproductive tract. This observation suggests the potential for sex steroids to influence neovascularization. Several other associations, including the predilection of certain diseases (such as Takayasu's arteritis and lupus, both of which involve endothelial cell proliferation) for premenopausal females, also imply the potential role of estrogen in angiogenesis. 1,2 The role of estradiol in uterine angiogenesis, mediated by at least 1 of the estrogen receptors, has been further suggested by findings in the estrogen receptor-␣ knockout mouse, in which angiogenesis is impaired, 3 and by the demonstration that estrogen receptor antagonists can inhibit angiogenesis. 4 The positive correlation between estrogen receptor expression, angiogenic activity, and breast tumor invasiveness also supports the angiogenic effect of estrogen mediated by the estrogen receptor(s). [5][6][7][8] Finally, some reports suggest that the antitumor effect of tamoxifen may in fact relate to an antiangiogenic action of this estrogen receptor agonist/antagonist. 9 Several additional lines of experimental evidence suggest that estrogen and other sex steroids play important roles in physiological and pathological angiogenesis. One of the first observations suggesting a hormonal influence on angiogenesis was an inhibitory effect on tumor vascularization by medroxyprogesterone. 10 Subsequent studies have indicated that the mechanism of this inhibition may relate to the regulation of thrombospondin-1, an angiogenesis inhibitor, by this hormone. 11 Angiogenesis has been noted to be a prognostic marker in breast cancer, 12 and inhibition of angiogenesis in these tumors has been effected by antiestrogens. 4 In addition, the estrogen metabolite 2-methoxyestradiol has been shown to be a potent antiangiogenic agent 13 mediated by actions on cytoskeletal structure 14 and by increasing endothelial cell apoptosis. 15,16 Vascular Endothelial Cell Proliferation and Migration Are Enhanced by EstradiolEstradiol induces endothelial proliferation and migration 17 mediated by t...

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Section: Postnatal Vasculogenesissupporting

confidence: 82%

Estrogen and Angiogenesis

Losordo

Isner

2001

ATVB

304

194

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“…30 Since the original report several other groups, including ours, have confirmed the original finding and have reported various modifications of the methods for the isolation, characterization, and culture of EPCs. 9,23,[31][32][33] The cells are thought to originate from a common hemangioblast precursor in the bone marrow; 9,33,34 however, nonhematopoietic mesenchymal precursors in the bone marrow (multipotent adult progenitor cells) have also been reported to transdifferentiate into EPCs in culture. 35 Other studies have reported that myeloid/monocyte lineage cells (CD14 ϩ ) can differentiate into cells with EPC characteristics.…”

Section: Isolation Characterization and Genetic Modification Of Epcsmentioning

confidence: 99%

“…Typically, the cells are defined on the basis of expression of cell surface markers such as CD34, Flk-1, and CD-133. 30,31 The cells have high proliferative potential, albeit for a finite number of cell divisions. 10,19 -21,30,34 As the cells differentiate, they acquire endothelial lineage markers, vascular endothelium-cadherin, PECAM-1 (CD31), von Willebrand factor, endothelial nitric oxide synthase (eNOS), and E-selectin, and incorporate acetylated low-density lipoprotein cholesterol.…”

Section: Isolation Characterization and Genetic Modification Of Epcsmentioning

confidence: 99%

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

et al. 2005

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Abstract-Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising. (Hypertension. 2005;46:7-18.)

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“…EPCs are a small population of progenitor cells that reside in bone marrow and, upon stimulation, are released into circulating peripheral blood [7][8][9][10][11]. Once in circulation, EPCs are thought to migrate to sites of vascular injury and are involved in vasculogenesis [12].…”

Section: Introductionmentioning

confidence: 99%

Toward Engineering a Human Neoendothelium with Circulating Progenitor Cells

et al. 2009

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Tissue-engineered vascular grafts may one day provide a solution to many of the limitations associated with using synthetic vascular grafts. However, identifying a suitable cell source and polymer scaffold to recreate the properties of a native blood vessel remains a challenge. In this work, we assess the feasibility of using endothelial progenitor cells (EPCs) found in circulating blood to generate a functional endothelium on poly(1,8-octanediol-co-citrate) (POC), a biodegradable elastomeric polyester. EPCs were isolated from human blood and biochemically differentiated into endothelial-like cells (HE-like) in vitro. The differentiated cell phenotype and function was confirmed by the appearance of the characteristic endothelial cell (EC) cobblestone morphology and positive staining for EC markers, von Willebrand factor, vascular endothelial cadherin, flk-1, and CD31. In addition, HE-like cells cultured on POC express endothelial nitric oxide synthase at levels comparable to aortic ECs. Furthermore, as with mature endothelial cells, HE-like cell populations show negligible expression of tissue factor. Similarly, HE-like cells produce and secrete prostacyclin and tissue plasminogen activator at levels comparable to venous and aortic ECs. When compared to fibroblast cells, HE-like cells cultured on POC show a decrease in the rate of plasma and wholeblood clot formation as well as a decrease in platelet adhesion. Finally, the data show that HE-like cells can withstand physiological shear stress of 10 dynes/cm 2 when cultured on POC-modified expanded poly(tetrafluoroethylene) vascular grafts. Collectively, these data are the foundation for future clinical studies in the creation of an autologous endothelial cell-seeded vascular graft. STEM CELLS 2010;28:318-328 Disclosure of potential conflicts of interest is found at the end of this article.

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Isolation of endothelial cells and their progenitor cells from human peripheral blood

Abstract: We conclude that endothelial progenitor cells can be isolated from human adult peripheral and umbilical cord blood and developed into EC cultures as a source of cells for vascular graft seeding and gene therapy.

Cited by 149 publications

References 26 publications

Estrogen and Angiogenesis

Estrogen and Angiogenesis

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

Toward Engineering a Human Neoendothelium with Circulating Progenitor Cells

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