A Pure Population of Lung Alveolar Epithelial Type II Cells Derived from Human Embryonic Stem Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Mar 16

PMID 17360544

Citations 97

Authors

Dachun Wang

David L Haviland

Alan R Burns

Eva Zsigmond

Rick A Wetsel

Affiliations

Soon will be listed here.

Abstract

Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute approximately 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.

Citing Articles

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

Eiken M, Childs C, Brastrom L, Frum T, Plaster E, Ahmed D Stem Cell Reports. 2024; 20(1):102376.

PMID: 39672155 PMC: 11784465. DOI: 10.1016/j.stemcr.2024.11.006.

Stem cell therapies for chronic obstructive pulmonary disease: mesenchymal stem cells as a promising treatment option.

Lai S, Guo Z Stem Cell Res Ther. 2024; 15(1):312.

PMID: 39300523 PMC: 11414322. DOI: 10.1186/s13287-024-03940-9.

Novel insights into the potential applications of stem cells in pulmonary hypertension therapy.

Guo S, Wang D Respir Res. 2024; 25(1):237.

PMID: 38849894 PMC: 11162078. DOI: 10.1186/s12931-024-02865-4.

Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model.

Fernandes R, Barbosa-Matos C, Borges-Pereira C, Carvalho A, Costa S Int J Mol Sci. 2024; 25(2).

PMID: 38279281 PMC: 10816825. DOI: 10.3390/ijms25021279.

Cartilage organoids and osteoarthritis research: a narrative review.

Zeng D, Chen Y, Liao Z, Wei G, Huang X, Liang R Front Bioeng Biotechnol. 2023; 11:1278692.

PMID: 38026876 PMC: 10666186. DOI: 10.3389/fbioe.2023.1278692.

References

Zheng B, Mills A, Bradley A . A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice. Nucleic Acids Res. 1999; 27(11):2354-60. PMC: 148802. DOI: 10.1093/nar/27.11.2354. View

Wobus A, Wallukat G, Hescheler J . Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers. Differentiation. 1991; 48(3):173-82. DOI: 10.1111/j.1432-0436.1991.tb00255.x. View

Wang G, Bunnell B, Painter R, Quiniones B, Tom S, Lanson Jr N . Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci U S A. 2004; 102(1):186-91. PMC: 544045. DOI: 10.1073/pnas.0406266102. View

Swystun V, Chen L, Factor P, Siroky B, Bell P, Matalon S . Apical trypsin increases ion transport and resistance by a phospholipase C-dependent rise of Ca2+. Am J Physiol Lung Cell Mol Physiol. 2005; 288(5):L820-30. DOI: 10.1152/ajplung.00396.2004. View

Van Vranken B, Romanska H, Polak J, Rippon H, Shannon J, Bishop A . Coculture of embryonic stem cells with pulmonary mesenchyme: a microenvironment that promotes differentiation of pulmonary epithelium. Tissue Eng. 2005; 11(7-8):1177-87. DOI: 10.1089/ten.2005.11.1177. View

Fang X, Song Y, Hirsch J, Galietta L, Pedemonte N, Zemans R . Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells. Am J Physiol Lung Cell Mol Physiol. 2005; 290(2):L242-9. DOI: 10.1152/ajplung.00178.2005. View

Mason R . Biology of alveolar type II cells. Respirology. 2006; 11 Suppl:S12-5. DOI: 10.1111/j.1440-1843.2006.00800.x. View

Rahpeymai Y, Hietala M, Wilhelmsson U, Fotheringham A, Davies I, Nilsson A . Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J. 2006; 25(6):1364-74. PMC: 1422160. DOI: 10.1038/sj.emboj.7601004. View

Samadikuchaksaraei A, Cohen S, Isaac K, Rippon H, Polak J, Bielby R . Derivation of distal airway epithelium from human embryonic stem cells. Tissue Eng. 2006; 12(4):867-75. DOI: 10.1089/ten.2006.12.867. View

10.

Rippon H, Polak J, Qin M, Bishop A . Derivation of distal lung epithelial progenitors from murine embryonic stem cells using a novel three-step differentiation protocol. Stem Cells. 2006; 24(5):1389-98. DOI: 10.1634/stemcells.2005-0465. View

11.

Samadikuchaksaraei A, Bishop A . Derivation and characterization of alveolar epithelial cells from murine embryonic stem cells in vitro. Methods Mol Biol. 2006; 330:233-48. DOI: 10.1385/1-59745-036-7:233. View

12.

Zhao Y, Andoh A, Shimada M, Takaya H, Hata K, Fujiyama Y . Secretion of complement components of the alternative pathway (C3 and factor B) by the human alveolar type II epithelial cell line A549. Int J Mol Med. 2000; 5(4):415-9. DOI: 10.3892/ijmm.5.4.415. View

13.

Kramer J, Hegert C, Guan K, Wobus A, Muller P, Rohwedel J . Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4. Mech Dev. 2000; 92(2):193-205. DOI: 10.1016/s0925-4773(99)00339-1. View

14.

Chroneos Z, Wert S, Livingston J, Hassett D, Whitsett J . Role of cystic fibrosis transmembrane conductance regulator in pulmonary clearance of Pseudomonas aeruginosa in vivo. J Immunol. 2000; 165(7):3941-50. DOI: 10.4049/jimmunol.165.7.3941. View

15.

Muller M, Fleischmann B, Selbert S, Ji G, Endl E, Middeler G . Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB J. 2000; 14(15):2540-8. DOI: 10.1096/fj.00-0002com. View

16.

Stearns R, Paulauskis J, Godleski J . Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol. 2001; 24(2):108-15. DOI: 10.1165/ajrcmb.24.2.4081. View

17.

Buttery L, Bourne S, Xynos J, Wood H, Hughes F, Hughes S . Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng. 2001; 7(1):89-99. DOI: 10.1089/107632700300003323. View

18.

Odorico J, Kaufman D, Thomson J . Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001; 19(3):193-204. DOI: 10.1634/stemcells.19-3-193. View

19.

Wobus A . Potential of embryonic stem cells. Mol Aspects Med. 2001; 22(3):149-64. DOI: 10.1016/s0098-2997(01)00006-1. View

20.

Nogee L, de Mello D, Dehner L, Colten H . Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med. 1993; 328(6):406-10. DOI: 10.1056/NEJM199302113280606. View