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Endothelial Progenitor Cells and Nitric Oxide: Matching Partners in Biomedicine

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Stem Cell Engineering

Abstract

Regeneration of damaged tissue by embryonic or adult stem cells has been and still is a topic of highest interest in experimental and clinical medicine. Adult stem cells have the ability to differentiate into a number of different cell types in dependence on their environment. Endothelial progenitor cells (EPCs) represent a population of adult stem cells. They contribute to the renewal of the largest organ of the body: the endothelium which is the inner layer of the vessel wall.

After an introduction into the topic of EPCs presenting the origin, fate, and biology of EPCs, we describe techniques of cell culture and bioassays for in vitro and in vivo testing of EPCs. Their applications in animal models and in humans are described to demonstrate the relevance of EPCs in cardiovascular medicine. On the other hand, nitric oxide (NO), a key player in cardiovascular biology, is introduced and the first findings describing the apparently powerful interactions between EPCs and NO are discussed. EPCs and NO seem to be the “Yin and Yang” of endothelial function and regeneration. We would like to illustrate recent findings of EPC biology with a special interest in their interaction with NO. Finally, we open the wide and interesting spectrum of further research activities in this field of biomedicine. If the differentiation of EPCs could be controlled in the laboratory, these cells may become the basis of cell-based therapies for cardiovascular disease. An interdisciplinary approach and the cooperation between scientists, engineers, and physicians will be able to transfer the findings of basic science into daily clinical application. Initial ideas and first steps for the realization of new concepts in EPC–NO research and therapeutic strategies with a special reference to bioengineering concepts are discussed.

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Abbreviations

BMS:

bare metal stents

BM:

bone marrow

BOOST:

Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration Trial

CVRFs:

cardiovascular risk factors

CFUs:

colony-forming units

CAD:

coronary artery disease

CRP:

C-reactive protein

cGMP:

cyclic guanosine monophosphate

DDAH:

dimethylarginine dimethylaminohydrolase

DES:

drug-eluting stents

ECs:

endothelial cells

eNOS; NOS III:

endothelial NOS

EPCs:

endothelial progenitor cells

Enos /– :

eNOS knockout mice

FAD:

flavin–adenine dinucleotide

FMN:

flavin mononucleotide

FACS:

fluorescence-activated cell sorting

GTP:

guanosine triphosphate

Hb:

hemoglobin

iNOS; NOS II:

inducible NOS

LDL:

low-density lipoprotein

MRI:

magnetic resonance imaging

MMP-9:

matrix metalloproteinase-9

MNCs:

mononuclear cells

nNOS; NOS I:

neuronal NOS

ADMA:

N G,N G-dimethylarginine (asymmetric dimethylarginine)

NHA:

N G-hydroxyl-l-arginine

l-NMA:

N G-monomethyl-l-arginine

l-NAME:

N G-nitro-l-arginine-methylester

NADPH:

nicotinamide adenine dinucleotide phosphate

NO:

nitric oxide

NOS:

nitric oxide synthase

PCI:

percutaneous coronary intervention

PAD:

peripheral artery disease

RBCs:

red blood cells

SMCs:

smooth muscle cells

SNO-Hb:

S-nitrosated derivative of oxygenated hemoglobin

SDF-1:

stromal cell-derived factor 1

\({\rm{O}}_{\rm{2}}^ -\) :

superoxide anions

SOD:

superoxide dismutase

BH4 :

Tetrahydrobiopterin

TACT:

therapeutic angiogenesis using cell transplantation

TOPCARE-AMI:

Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction

VEGF:

vascular endothelial growth factor

WT:

wild-type mice

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Keymel, S., Özüyaman, B., Grau, M., Kelm, M., Kleinbongard, P. (2011). Endothelial Progenitor Cells and Nitric Oxide: Matching Partners in Biomedicine. In: Artmann, G., Minger, S., Hescheler, J. (eds) Stem Cell Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11865-4_10

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