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Role of Progenitors in Pulmonary Fibrosis and Asthma

  • Chapter
Lung Stem Cells in the Epithelium and Vasculature

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

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Abstract

Damage to the airway epithelium in a variety of pulmonary disorders, including asthma and idiopathic pulmonary fibrosis (IPF), leads to remodeling changes that impair lung function. Lung injury elicits the recruitment of stem cells and other progenitor cells and fibrocytes to the airways. These cells proliferate and differentiate into fibroblasts and myofibrolasts that secrete collagen and other extracellular matrix components that damage the normal airway architecture in a process termed airway remodeling. In IPF, the progressive scarring in the airways leads to irreversible pulmonary fibrosis. Stem cells are a potential source of pluripotent cells to regenerate lost cells in the airways and restore lung function. Stem cell niches in lung are specialized compartments where pluripotent stem cells reside in a defined stromal environment; stem cells mobilized from these sites may help restore lung structure after injury. Recent studies indicate that embryonic stem cells (ESCs) can be differentiated in vitro to lung lineage-specific cells to repair lung injury. Our understanding of the factors controlling stem cell migration to the lungs from the hematopoietic compartment, the development of stem cells locally in lung niches, and the transformation of stem cells to specific lung-lineage cell types is rapidly advancing. This information will be key for realizing how best to control the growth and differentiation of these progenitor cells ex vivo for therapeutic benefit in patients with progressive lung disorders.

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Abbreviations

αSMA:

Alpha smooth muscle actin

ABC:

ATP-binding cassette

ADSC:

Adipose stromal cell

AFSC:

Amniotic fluid stem cell

AQP-1:

Aquaporin 1

AQP-5:

Aquaporin 5

AT1:

Alveolar type 1

AT2:

Alveolar type 2

BADJ:

Bronchoalveolar duct junction

BAL:

Bronchoalveolar lavage

BASC:

Bronchioalveolar stem cell

BEGM:

Bronchial epithelial growth medium

BM-MSC:

Bone marrow-derived mesenchymal stem cell

BRDU:

Bromodeoxyuridine

CBP:

CREB-binding protein

CC-10:

Club cell-specific protein

CCL5:

Chemokine (C–C motif) ligand 5

CCL11:

Chemokine (C–C motif) ligand 11

CCL12:

Chemokine (C–C motif) ligand 12

CCL17:

Chemokine (C–C motif) ligand 17

CCL24:

Chemokine (C–C motif) ligand 24

CCR2:

Chemokine (C–C motif) receptor 2

CCSP:

Club cell-specific promoter

CD31:

Cluster of differentiation 31

CD34:

Cluster of differentiation 34

CD45:

Cluster of differentiation 45

CD147:

Cluster of differentiation 147

CD206:

Cluster of differentiation 206

CK5:

Cytokeratin 5

CysLT:

Cysteinyl leukotriene

CysLT1R:

Cysteinyl leukotriene 1 receptor

CXCR4:

Chemokine (C-X-C motif) receptor 4

CXCL1:

Chemokine (C-X-C motif) ligand 1

CXCL12:

Chemokine (C-X-C motif) ligand 12

DAB:

3,3′-Diaminobenzidine

ECFC:

Endothelial colony-forming cell

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular signal-regulated kinase

ESC:

Embryonic stem cell

Fgf10:

Fibroblast growth factor 10

FGF:

Fibroblast growth factor

hESC:

Human embryonic stem cell

HIF-1α:

Hypoxia-inducible factor 1 alpha

HIF-2α:

Hypoxia-inducible factor 2 alpha

ICAM:

Intracellular adhesion molecule 1

IL-4:

Interleukin 4

IL-5:

Interleukin 5

IL-6:

Interleukin 6

IL-12:

Interleukin 12

IL-13:

Interleukin 13

IL-33:

Interleukin 33

IFN-γ:

Interferon-γ

IPF:

Idiopathic pulmonary fibrosis

iPSC:

Induced pluripotent stem cell

JNK:

Jun amino-terminal kinase

KDR:

Vascular endothelial growth factor receptor2

KGF:

Keratinocyte growth factor

Klf-4:

Kruppel-like factor 4

LEF-1:

Lymphoid enhancer factor-1

LRC:

Label-retaining cell

MMP:

Matrix metalloproteinase

MMP-2:

Matrix metalloproteinase 2

MMP-3:

Matrix metalloproteinase 3

MMP-7:

Matrix metalloproteinase 7

MRC1:

Mannose receptor (cluster of differentiation 206)

MSC:

Mesenchymal stem cell

Nf-κB:

Nuclear factor kappa B

OVA:

Ovalbumin

PDGF:

Platelet-derived growth factor

SAGM:

Small airways growth medium

SDF-1:

Stromal-derived factor 1

SP:

Side population

SPC:

Surfactant protein C

SPD:

Surfactant protein D

ST2L:

Interleukin 33 receptor component

SVP:

Stromal vascular fraction

TCF:

T cell factor

TGF-β:

Transforming growth factor beta

Th1:

T-helper type 1

Th2:

T-helper type 2

Th17:

T-helper type 17

VEGF:

Vascular endothelial growth factor

VEGF-A:

Vascular endothelial growth factor A

WISP-1:

Wnt1-inducible-signaling pathway protein 1

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Authors and Affiliations

  1. Department of Zoology, Immunology and Regenerative Medicine Research Unit, Laboratory Room 214, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700 019, India

    Ena Ray Banerjee Ph.D.

  2. Department of Medicine, Center for Allergy and Inflammation, UW Medicine at South Lake Union, University of Washington, Brotman Building, Room 253, 850 Republican Street, Seattle, WA, 98109-4725, USA

    William Reed Henderson Jr. M.D.

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  1. Ena Ray Banerjee Ph.D.
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  2. William Reed Henderson Jr. M.D.
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Correspondence to Ena Ray Banerjee Ph.D. .

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Editors and Affiliations

  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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Ray Banerjee, E., Henderson, W.R. (2015). Role of Progenitors in Pulmonary Fibrosis and Asthma. 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_5

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