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Published online on March 2, 2007, 10.1073/pnas.0700052104
PNAS | March 13, 2007 | vol. 104 | no. 11 | 4449-4454


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BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY
A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells

Dachun Wang*, David L. Haviland*, Alan R. Burns{dagger}, Eva Zsigmond{ddagger}, and Rick A. Wetsel*,{ddagger},§,¶

*Research Center for Immunology and Autoimmune Diseases and {ddagger}Laboratory for Developmental Biology, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center, Houston, TX 77030; §Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, TX 77030; and {dagger}Cardiovascular Sciences Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030

Communicated by C. Thomas Caskey, University of Texas Health Science Center, Houston, TX, January 4, 2007 (received for review November 22, 2006)

Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute {approx}60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (>99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, {alpha}-1-antitrypsin, and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung.

complement | differentiation | surfactant proteins | {alpha}-1-antitrypsin | cystic fibrosis transmembrane conductance receptor

Author contributions: D.W. and R.A.W. designed research; D.W., D.L.H., A.R.B., and E.Z. performed research; D.W., A.R.B., and R.A.W. analyzed data; and D.W. and R.A.W. wrote the paper.

The authors declare no conflict of interest.

To whom correspondence should be addressed at: The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center, 1825 Pressler Street, Houston, TX 77030. E-mail: rick.a.wetsel{at}uth.tmc.edu

© 2007 by The National Academy of Sciences of the USA


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