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The Use of Embryonic Stem Cells and Induced Pluripotent Stem Cells to Model Pulmonary Arterial Hypertension

  • Chapter
Lung Stem Cells in the Epithelium and Vasculature

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

Abstract

Elucidating alterations in gene expression and cell signaling is essential for understanding the molecular basis for pulmonary arterial hypertension (PAH). Transcriptomic differences, which affect cell function, increase the risk for development of PAH. The use of animal models of disease and studies of end stage PAH tissue samples has significantly furthered the progress in human PAH research over the last century; however, both experimental sources have major limitations including end stage disease and limited translation to human patients. The ongoing challenge is to translate these findings into patient therapies. The ability to validate transformative therapies will require human tissue and cells, a limited resource under the best of circumstances. This need to study disease in multiple cell and tissue types has fostered significant interest in the use of modified embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to model lung disease. These cells provide an alternative for studying the initiation and genetic basis of disease processes in both heritable and idiopathic PAH. In this Chapter, we will focus on the use of murine ESCs and murine and patient-derived iPSCs in pulmonary vascular disease research as a model for PAH.

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Abbreviations

BMPR2:

Bone morphogenic protein (receptor 2)

COPD:

Chronic obstructive pulmonary disease

EC:

Endothelial cell

ESC:

Embryonic stem cells

EUCOMM:

European conditional mouse mutagenesis program

FLK-1/KDR:

Fetal liver kinase-1/Kinase insert domain receptor

HPAH:

Hereditary pulmonary arterial hypertension

IPAH:

Idiopathic pulmonary arterial hypertension

iPSC:

Induced pluripotent stem cells

KOMP-ES:

Knockout mouse project-embryonic stem cell repository

L-EPC:

Late outgrowth endothelial progenitor cell

MPSVII:

Mucopolysaccharidosis

MSC:

Mesenchymal stromal cell

NIH:

National Institute of Health

PAH:

Pulmonary arterial hypertension

PF:

Pulmonary fibrosis

PRDC:

Protein related to DAN and cerberus

RV:

Right ventricular

SCNT:

Somatic cell nuclear transfer

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was funded by grants to S.M. Majka from the NIH NHLBI R01HL091105 and R01HL11659701. We would like to extend our gratitude to Dr. Darrell Kotton for the creation of the first BMPR2 mutant iPSC lines submitted to the Vanderbilt University repository (BMP3a and BMP1a).

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Authors and Affiliations

  1. Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, TN, USA

    Anna R. Hemnes

  2. Department of Pediatrics, Vanderbilt University, Nashville, TN, USA

    Eric D. Austin

  3. Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt Center for Stem Cell Biology, Cell and Developmental Biology, Vanderbilt University, P475 MRBIV/Langford, 2213 Garland Ave, Nashville, TN, 37232, USA

    Susan Majka Ph.D.

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  1. Anna R. Hemnes
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Correspondence to Susan Majka 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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Hemnes, A.R., Austin, E.D., Majka, S. (2015). The Use of Embryonic Stem Cells and Induced Pluripotent Stem Cells to Model 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_18

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