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Vascular Repair and Regeneration by Endothelial Progenitor Cells

  • Chapter
Lung Stem Cells in the Epithelium and Vasculature

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 843 Accesses

Abstract

Pulmonary arterial endothelial cells perform a plethora of functions including forming an antithrombotic surface and regulating blood flow by the release of paracrine factors that can constrict or dilate the vasculature to allow a matching between ventilation and perfusion. Moreover, inflammatory processes in the lung depend on leukocytes migrating through the endothelial monolayer. Disruption of the endothelial barrier function leads to edema formation in acute lung injury (ALI), and persistent endothelial dysfunction also plays an important role in the onset of pulmonary arterial hypertension (PAH).

Endothelial cells have some capacity for repair, but this is not always sufficient. Therefore, regenerative endothelial progenitor cells (EPCs) have attracted considerable attention as a way to enhance endothelial regeneration. The ability of EPCs to mediate neovascularization and repair vessels after injury has been demonstrated in animal models of myocardial infarction, hind limb ischemia, and wound healing. Recent findings also indicate that EPCs could be involved in pulmonary vascular repair and in this chapter, we will discuss the experiments that have been performed to establish the importance and therapeutic potential of EPCs in bronchopulmonary dysplasia, PAH, ALI, and chronic obstructive pulmonary disease (COPD). Besides their therapeutic relevance, studying EPC numbers and functionality may also provide insights into the underlying disease pathology and serve as prognostic markers for disease outcomes.

After a summary of how EPCs were discovered and how they might be used for vascular repair, we will discuss results from experimental and clinical studies of pulmonary disease and also indicate the areas that deserve further investigation.

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Abbreviations

ALI:

Acute lung injury

BMPR2:

Bone morphogenetic protein receptor 2

BPD:

Bronchopulmonary dysplasia

Cdc42:

Cell division control protein 42 homolog

COPD:

Chronic obstructive pulmonary disease

CXCR4:

C-X-C Chemokine receptor type 4

ECFCs:

Endothelial colony-forming cells

eNOS:

Endothelial nitric oxide synthase

EPC:

Endothelial progenitor cell

FoxM1:

Forkhead box protein M1

HGF:

Hepatocyte growth factor

IGF1:

Insulin-like growth factor 1

IL10:

Interleukin 10

IPAH:

Idiopathic pulmonary arterial hypertension

LPS:

Lipopolysaccharide

MCP1:

Monocyte chemoattractant protein-1

MSC:

Mesenchymal stem cell

NYHA:

New York Heart Association

PAEC:

Pulmonary artery endothelial cell

PAH:

Pulmonary arterial hypertension

PDE5:

Phosphodiesterase 5

Rac1:

Ras-related C3 botulinum toxin substrate 1

SDF1:

Stromal cell-derived factor 1

VEGF:

Vascular endothelial growth factor

VEGFR-2:

Vascular endothelial growth factor receptor 2

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Acknowledgements

This work was supported by a Parker B. Francis fellowship (G.M.) and grants from the National Institutes of Health HL090152 (A.B.M.), GM094220 (J.R.), and HL118068 (A.B.M. and J.R.).

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, University of Illinois, 835 S. Wolcott, Chicago, IL, 60612, USA

    Glenn Marsboom, Min Zhang, Jalees Rehman & Asrar B. Malik Ph.D.

  2. Center for Lung and Vascular Biology, University of Illinois, Chicago, IL, USA

    Glenn Marsboom, Min Zhang, Jalees Rehman & Asrar B. Malik Ph.D.

  3. Department of Medicine, Section of Cardiology, University of Illinois, Chicago, IL, USA

    Jalees Rehman

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  1. Glenn Marsboom
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  2. Min Zhang
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  4. Asrar B. Malik Ph.D.
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Correspondence to Asrar B. Malik Ph.D. .

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  1. Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA

    Amy Firth

  2. Department of Medicine, The Univsersity of Arizona, Tucson, Arizona, USA

    Jason X.-J. Yuan

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Marsboom, G., Zhang, M., Rehman, J., Malik, A.B. (2015). Vascular Repair and Regeneration by Endothelial Progenitor Cells. 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_17

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