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Ex Vivo Lung Bioengineering

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Lung Stem Cells in the Epithelium and Vasculature

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

Abstract

Chronic lung diseases are devastating diseases that are increasing in prevalence. Most have no cure and lung transplantation remains the only available therapeutic option. However, the number of suitable donor lungs is inadequate to meet current clinical demands and thus alternative options are desperately needed. There are a number of conceptually viable alternatives for generating functional pulmonary tissue ex vivo, including the use of either biologic or synthetic scaffolds coupled with an appropriate recellularization and ex vivo culture strategy. Biologic lung scaffolds have been generated using several different perfusion-based decellularization techniques. Whole organ decellularization aims to selectively remove cells while maintaining native tissue macro and microarchitecture. Alternatively, synthetic materials, coupled with advanced manufacturing techniques, could be used to generate a completely artificial scaffold with the necessary biologic properties to permit regeneration of functional lung tissue. Either a biologic or synthetic scaffold could then be subsequently recellularized with autologous cells, thus eradicating the immunological complications frequently accompanying organ transplantation. These approaches are a promising alternative to overcoming the chronic shortage of donor organs.

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Abbreviations

2D:

Two-dimensional

3D:

Three-dimensional

α-SMA:

Alpha smooth muscle actin

A549:

Adenocarcinomic human alveolar basal epithelial cells

A9:

Transformed subcutaneous murine fibroblasts

AFM:

Atomic force microscopy

ALI:

Air-liquid-interface

ATI:

Type 1 alveolar epithelial cells

ATII:

Type 2 alveolar epithelial cells

Aqp5:

Aquaporin 5

BMMSCs:

Porcine bone marrow-derived mesenchymal stem cells

C10:

Immortalized murine alveolar epithelial cells

CaCl2 :

Calcium chloride

CBF12:

Human endothelial progenitor cells

CC10:

Club Cell 10 kDa Protein (=CCSP)

CCSP:

Club cell secretory protein (=CC10)

CD:

Cluster of differentiation

CD206:

Mannose receptor C 1 (cluster of differentiation factor 206)

CHAPS:

3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate

Ck:

Cytokeratin

cmH2O:

Centimeters of water (pressure)

Col1α1:

Collagen 1

COPD:

Chronic obstructive pulmonary disease

CT:

Computed tomography

Ctnnb1:

Beta catenin

DAPI:

4′,6-diamidino-2-phenylindole

DMEM:

Dulbecco’s modified Eagle’s medium

DNA:

Deoxyribonucleic acid

DNase:

Deoxyribonuclease

E17:

Embryonic day 17

ECM:

Extracellular matrix

EDTA:

Ethylenediaminetetracetic acid

ESC:

Embryonic stem cells

EVLP:

Ex vivo lung perfusion

FBS:

Fetal bovine serum

FDA:

Food and Drug Administration

GAGS:

Glycosaminoglycans

GFP:

Green fluorescent protein

H&E:

Hematoxylin–eosin

H2O:

Water

hAEC:

Human alveolar epithelial cells

hAT-MSC:

Human adipose-derived mesenchymal stem cells

hBE:

Human bronchial epithelial cells

hBM-MSC:

Human bone marrow-derived mesenchymal stem cells

hFLC:

Human fetal lung cells

hiPS:

Human induced pluripotent cells

hLF:

Human lung fibroblasts

hMSC:

Human bone marrow-derived mesenchymal stem cells

HUVEC:

Human umbilical vein endothelial cells

IPF:

Idiopathic pulmonary fibrosis

iPS:

Induced pluripotent stem cells

mESCs:

Murine embryonic stem cells

MgSO4 :

Magnesium sulfate

mM:

Millimolar

mmHg:

Millimeters of mercury

MRC5:

Human fetal lung fibroblast cell line

MSC:

Mesenchymal stem cells

NaCl:

Sodium chloride

NaHCO3 :

Sodium bicarbonate

Nkx2-1:

Nkx2 homeobox 1 protein (aka TTF1—thyroid transcription factor 1)

PAEC:

Pulmonary alveolar epithelial cells

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

PDGFRα:

Platelet derived growth factor receptor alpha

RGD:

Arg-Gly-Asp

rhCHI3L1:

Recombinant human chitinase 3-like 1 protein

RNase:

Ribonuclease

SAEC:

Small airway epithelial cells

SDC:

Sodium deoxycholate

SDS:

Sodium dodecyl sulfate

SEM:

Scanning electron microscopy

SPA:

Surfactant protein A

SPC:

Surfactant protein C

TEM:

Transmission electron microscopy

T1α:

T1alpha, podoplanin

TGF-β:

Transforming growth factor beta

Ttf-1:

Thyroid transcription factor 1 (Nkx2.1)

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Comprehensive Pneumology Center, Munich, Germany

    Darcy E. Wagner, Franziska E. Uhl & Melanie Königshoff

  2. Department of Medicine, Pulmonary and Critical Care, University of Vermont, 149 Beaumont Avenue, Room 226 Health Sciences Research Facility, Burlington, VT, 05405, USA

    Daniel J. Weiss

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  1. Darcy E. Wagner
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  2. Franziska E. Uhl
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  3. Melanie Königshoff
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  4. Daniel J. Weiss
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Correspondence to Daniel J. Weiss .

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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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Wagner, D.E., Uhl, F.E., Königshoff, M., Weiss, D.J. (2015). Ex Vivo Lung Bioengineering. 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_8

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