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Endothelial Colony-Forming Cells in Pulmonary Arterial Hypertension

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Lung Stem Cells in the Epithelium and Vasculature

Abstract

The search for stem/progenitor cells capable of endothelium regeneration during postnatal life has gained substantial interest over the past decades and led to the discovery of a subset of cells with robust endothelial regenerative capacity. These so-called endothelial colony-forming cells (ECFCs) are phenotypically identical to cultured endothelial cells, but exhibit high proliferative potential, capacity for self-regeneration, and in vivo vasculogenesis potential. ECFCs have been isolated from endothelial cells from several tissues and are rare in the peripheral blood circulation. Our understanding of ECFC biology in disease is at an early stage. In pulmonary arterial hypertension, there is evidence for both beneficial and pathological roles of ECFCs. A favorable ECFC response repairs endothelial cell dysfunction and attenuates right ventricular hypertrophy. In situations with sustained endothelial stress or uncontrolled propagation of a reparative response, proliferation of ECFCs contributes to pathological remodeling.

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Abbreviations

CD:

Cluster designation

CXCR-4:

Chemokine (C-X-C motif) receptor 4

DiI-Ac-LDL:

1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate acetylated-low density lipoprotein

ECFC:

Endothelial colony-forming cells

EGM-2:

Endothelial growth medium-2

eNOS:

Endothelial nitric oxide synthase

Flt-1:

FMS-like tyrosine kinas-1

HUVEC:

Human umbilical vein endothelial cell

KDR:

Kinase insert domain receptor

lacZ:

Lactose operon-Z

NOD/SCID:

Nonobese diabetic/severe combined immunodeficiency

SMC:

Smooth muscle cells

VE-cadherin:

Vascular endothelium-cadherin

vWF:

von Willebrand factor

WKYMVm:

Stands for peptide strand structure Trp-Lys-Tyr-Met-Val-D-Met-NH2

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Acknowledgments

Illustration by David Schumick, B.S., CMI. Reprinted with the permission of the Cleveland Clinic Center for Medical Art and Photography © 2014. All Rights Reserved. Kewal Asosingh is a Scholar of the International Society for Advancement of Cytometry (ISAC). This work was supported by grants HL60917, HL115008, and M01 RR018390 from the National Institutes of Health, American Thoracic Society/Pulmonary Association Research grant (PH-07-003), and the Hematopoietic Stem Cell Core Facility of the Case Comprehensive Cancer Center (P30 CA43703).

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Correspondence to Kewal Asosingh Ph.D. or Serpil Erzurum M.D. .

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Asosingh, K., Rose, J., Erzurum, S. (2015). Endothelial Colony-Forming Cells in Pulmonary Arterial Hypertension. In: Firth, A., Yuan, JJ. (eds) Lung Stem Cells in the Epithelium and Vasculature. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-16232-4_9

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