title: Assessment of cell line models of primary human cells by Raman spectral phenotyping.
abstract: Researchers have previously questioned the suitability of cell lines as models for primary cells. In this study, we used Raman microspectroscopy to characterize live A549 cells from a unique molecular biochemical perspective to shed light on their suitability as a model for primary human pulmonary alveolar type II (ATII) cells. We also investigated a recently developed transduced type I (TT1) cell line as a model for alveolar type I (ATI) cells. Single-cell Raman spectra provide unique biomolecular fingerprints that can be used to characterize cellular phenotypes. A multivariate statistical analysis of Raman spectra indicated that the spectra of A549 and TT1 cells are characterized by significantly lower phospholipid content compared to ATII and ATI spectra because their cytoplasm contains fewer surfactant lamellar bodies. Furthermore, we found that A549 spectra are statistically more similar to ATI spectra than to ATII spectra. The spectral variation permitted phenotypic classification of cells based on Raman spectral signatures with >99% accuracy. These results suggest that A549 cells are not a good model for ATII cells, but TT1 cells do provide a reasonable model for ATI cells. The findings have far-reaching implications for the assessment of cell lines as suitable primary cellular models in live cultures.
authors.affiliation: Department of Materials, Imperial College London, London, United Kingdom.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Swain
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Kemp
authors.forename: Peter
authors.initials: P
authors.lastname: Goldstraw
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
mesh_terms: D002460:Cell Line; D048430:Cell Shape; D002470:Cell Survival; D016002:Discriminant Analysis; D006801:Humans; D008168:Lung / Q000166:cytology; D008954:Models, Biological; D010641:Phenotype; D010713:Phosphatidylcholines / Q000378:metabolism; D025341:Principal Component Analysis; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D010713:Phosphatidylcholines
references.citation: Analyst. 2004 Oct;129(10):880-5
references.pmid: 15457314
references.citation: Biochem Biophys Res Commun. 1999 Sep 7;262(3):744-51
references.pmid: 10471396
references.citation: Exp Lung Res. 1984;6(3-4):197-213
references.pmid: 6092046
references.citation: J Biochem. 2006 May;139(5):821-9
references.pmid: 16751589
references.citation: Am J Respir Cell Mol Biol. 2004 Apr;30(4):500-9
references.pmid: 15033639
references.citation: Int J Cancer. 1976 Jan 15;17(1):62-70
references.pmid: 175022
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Apr;282(4):L684-92
references.pmid: 11880293
references.citation: J Cell Biochem. 2006 Sep 1;99(1):178-86
references.pmid: 16598770
references.citation: Food Chem Toxicol. 1992 Sep;30(9):789-94
references.pmid: 1427517
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):646-51
references.pmid: 11209060
references.citation: Anal Chem. 2004 Jun 1;76(11):3185-93
references.pmid: 15167800
references.citation: Exp Cell Res. 1991 Aug;195(2):361-7
references.pmid: 2070819
references.citation: Circulation. 2002 Dec 10;106(24):3009-17
references.pmid: 12473544
references.citation: Am J Respir Cell Mol Biol. 1996 Aug;15(2):224-31
references.pmid: 8703478
references.citation: Pharm Res. 1995 Aug;12(8):1115-9
references.pmid: 7494821
references.citation: Biopolymers. 2004 May-Jun 5;74(1-2):157-62
references.pmid: 15137115
references.citation: Br J Cancer. 1995 Feb;71(2):232-9
references.pmid: 7841035
references.citation: Bone. 1994 Nov-Dec;15(6):585-91
references.pmid: 7873286
references.citation: Biophys J. 2008 Dec 15;95(12):5978-87
references.pmid: 18820234
references.citation: Cell Tissue Res. 2003 Jan;311(1):31-45
references.pmid: 12483282
references.citation: Exp Cell Res. 1998 Sep 15;243(2):359-66
references.pmid: 9743595
references.citation: J Cell Biochem. 2008 Jul 1;104(4):1427-38
references.pmid: 18348254
references.citation: J Natl Cancer Inst. 1973 Nov;51(5):1417-23
references.pmid: 4357758
references.citation: Am J Respir Cell Mol Biol. 2008 Nov;39(5):591-7
references.pmid: 18539954
references.citation: Nat Mater. 2009 Sep;8(9):763-70
references.pmid: 19633661
references.citation: Am J Respir Cell Mol Biol. 1997 Dec;17(6):672-82
references.pmid: 9409554
references.citation: Science. 1993 May 14;260(5110):920-6
references.pmid: 8493529
references.citation: Biophys J. 2007 Jul 15;93(2):668-73
references.pmid: 17468162
references.citation: Anal Chem. 2003 Feb 1;75(3):394-404
references.pmid: 12585463
references.citation: J Cell Biochem. 2004 Aug 15;92(6):1180-92
references.pmid: 15258901
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10159-64
references.pmid: 16002471
references.citation: J Biomed Opt. 2005 May-Jun;10(3):031106
references.pmid: 16229631
references.citation: Br J Cancer. 2005 Jun 20;92(12):2166-70
references.pmid: 15928665
references.citation: Biochim Biophys Acta. 1980 Jan 18;617(1):36-50
references.pmid: 6243488
references.citation: Microsc Res Tech. 1997 Sep 1;38(5):488-99
references.pmid: 9376652
references.citation: Nature. 1990 Sep 20;347(6290):301-3
references.pmid: 2205805