Stem Cells and Cell–Matrix Interactions in Lung

  • Viranuj Sueblinvong
  • Jesse RomanEmail author
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Stem cells have become the focus of many investigations owing to emerging data implicating their role in normal physiological processes and as potential targets for the development of therapeutic interventions. The factors that control the functions of stem cells related to migration, homing, and differentiation, among others, remain incompletely elucidated, but it is evident that, like other cells, stem cells express receptors that recognize signals from their immediate microenvironment. One such set of signals comes from the stroma, which contains several types of extracellular matrix components (e.g., fibronectin, collagens, proteoglycans). Stem cells express functional matrix-binding receptors of the integrin family and, therefore, the relative composition of the extracellular matrix is likely to be an important determinant of stem cell behavior. This is critical since the relative tissue composition of the extracellular matrix changes depending on developmental stage. Furthermore, inflammation during injury results in extracellular matrix remodeling and so does cancer formation. Thus, the alterations in matrix expression and turnover that occur during the lifetime of an animal are likely to contribute to the various signals that influence stem cell function. Although there are studies that support this idea, this field is not mature and, consequently, the exact role of cell–stroma interactions in stem cell biology remains undefined. This chapter summarizes the limited data available in this area with the hope of stimulating much needed research designed to elucidate how cell–stroma interactions affect stem cell functions in normal and disease states, and how these events can be manipulated pharmacologically to improve clinical outcomes.


Lung extracellular matrix Integrin receptors Lung development Cancer stem cells 


  1. 1.
    Nguyen NM, and Senior RM. Laminin isoforms and lung development: all isoforms are not equal. Dev Biol 2006; 294:271–279.PubMedCrossRefGoogle Scholar
  2. 2.
    Roman J. Extracellular matrix and lung inflammation. Immunol Res 1996; 15:163–178.PubMedCrossRefGoogle Scholar
  3. 3.
    Dunsmore SE, and Rannels DE. Extracellular matrix biology in the lung. Am J Physiol 1996; 270:L3–L27.PubMedGoogle Scholar
  4. 4.
    Montes GS. Structural biology of the fibres of the collagenous and elastic systems. Cell Biol Int 1996; 20:15–27.PubMedCrossRefGoogle Scholar
  5. 5.
    Calabresi C, Arosio B, Galimberti L, Scanziani E, Bergottini R, Annoni G, and Vergani C. Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung. Exp Gerontol 2007; 42:1003–1011.PubMedCrossRefGoogle Scholar
  6. 6.
    McGowan SE. Extracellular matrix and the regulation of lung development and repair. FASEB J 1992; 6:2895–2904.PubMedGoogle Scholar
  7. 7.
    Ito K, and Barnes PJ. COPD as a disease of accelerated lung aging. Chest 2009; 135:173–180.PubMedCrossRefGoogle Scholar
  8. 8.
    Negrini D, Passi A, and Moriondo A. The role of proteoglycans in pulmonary edema development. Intensive Care Med 2008; 34:610–618.PubMedCrossRefGoogle Scholar
  9. 9.
    Iozzo RV, and Murdoch AD. Proteoglycans of the extracellular environment: clues from the gene and protein side offer novel perspectives in molecular diversity and function. FASEB J 1996; 10:598–614.PubMedGoogle Scholar
  10. 10.
    Miner JH, and Yurchenco PD. Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol 2004; 20:255–284.PubMedCrossRefGoogle Scholar
  11. 11.
    Relan NK, and Schuger L. Basement membranes in development. Pediatr Dev Pathol 1999; 2:103–118.PubMedCrossRefGoogle Scholar
  12. 12.
    Patton BL, Miner JH, Chiu AY, and Sanes JR. Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol 1997; 139:1507–1521.PubMedCrossRefGoogle Scholar
  13. 13.
    Bolcato-Bellemin AL, Lefebvre O, Arnold C, Sorokin L, Miner JH, Kedinger M, and Simon-Assmann P. Laminin alpha5 chain is required for intestinal smooth muscle development. Dev Biol 2003; 260:376–390.PubMedCrossRefGoogle Scholar
  14. 14.
    Nguyen NM, Miner JH, Pierce RA, and Senior RM. Laminin alpha 5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung. Dev Biol 2002; 246:231–244.PubMedCrossRefGoogle Scholar
  15. 15.
    Miner JH, Patton BL, Lentz SI, Gilbert DJ, Snider WD, Jenkins NA, Copeland NG, and Sanes JR. The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8–11, and cloning of a novel alpha3 isoform. J Cell Biol 1997; 137:685–701.PubMedCrossRefGoogle Scholar
  16. 16.
    Schuger L, Skubitz AP, Gilbride K, Mandel R, and He L. Laminin and heparan sulfate proteoglycan mediate epithelial cell polarization in organotypic cultures of embryonic lung cells: evidence implicating involvement of the inner globular region of laminin beta 1 chain and the heparan sulfate groups of heparan sulfate proteoglycan. Dev Biol 1996; 179:264–273.PubMedCrossRefGoogle Scholar
  17. 17.
    Pankov R, and Yamada KM. Fibronectin at a glance. J Cell Sci 2002; 115:3861–3863.PubMedCrossRefGoogle Scholar
  18. 18.
    Schwarzbauer JE, Patel RS, Fonda D, and Hynes RO. Multiple sites of alternative splicing of the rat fibronectin gene transcript. EMBO J 1987; 6:2573–2580.PubMedGoogle Scholar
  19. 19.
    Williams DA, Rios M, Stephens C, and Patel VP. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. Nature 1991; 352:438–441.PubMedCrossRefGoogle Scholar
  20. 20.
    Magnuson VL, Young M, Schattenberg DG, Mancini MA, Chen DL, Steffensen B, and Klebe RJ. The alternative splicing of fibronectin pre-mRNA is altered during aging and in response to growth factors. J Biol Chem 1991; 266:14654–14662.PubMedGoogle Scholar
  21. 21.
    Mosher DF, Sottile J, Wu C, and McDonald JA. Assembly of extracellular matrix. Curr Opin Cell Biol 1992; 4:810–818.PubMedCrossRefGoogle Scholar
  22. 22.
    Hocking DC. Fibronectin matrix deposition and cell contractility: implications for airway remodeling in asthma. Chest 2002; 122:275S–278S.PubMedCrossRefGoogle Scholar
  23. 23.
    Midwood KS, Mao Y, Hsia HC, Valenick LV, and Schwarzbauer JE. Modulation of cell-fibronectin matrix interactions during tissue repair. J Investig Dermatol Symp Proc 2006; 11:73–78.PubMedCrossRefGoogle Scholar
  24. 24.
    Bitterman PB, Rennard SI, Adelberg S, and Crystal RG. Role of fibronectin as a growth factor for fibroblasts. J Cell Biol 1983; 97:1925–1932.PubMedCrossRefGoogle Scholar
  25. 25.
    Muro AF, Chauhan AK, Gajovic S, Iaconcig A, Porro F, Stanta G, and Baralle FE. Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan. J Cell Biol 2003; 162:149–160.PubMedCrossRefGoogle Scholar
  26. 26.
    McDonald JA, Kelley DG, and Broekelmann TJ. Role of fibronectin in collagen deposition: Fab’ to the gelatin-binding domain of fibronectin inhibits both fibronectin and collagen organization in fibroblast extracellular matrix. J Cell Biol 1982; 92:485–492.PubMedCrossRefGoogle Scholar
  27. 27.
    Aguilar S, Nye E, Chan J, Loebinger M, Spencer-Dene B, Fisk N, Stamp G, Bonnet D, and Janes SM. Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells 2007; 25:1586–1594.PubMedCrossRefGoogle Scholar
  28. 28.
    Muro AF, Moretti FA, Moore BB, Yan M, Atrasz RG, Wilke CA, Flaherty KR, Martinez FJ, Tsui JL, Sheppard D et al. An essential role for fibronectin extra type III domain A in pulmonary fibrosis. Am J Respir Crit Care Med 2008; 177:638–645.PubMedCrossRefGoogle Scholar
  29. 29.
    Hynes RO. Integrins: a family of cell surface receptors. Cell 1987; 48:549–554.PubMedCrossRefGoogle Scholar
  30. 30.
    Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992; 69:11–25.PubMedCrossRefGoogle Scholar
  31. 31.
    Miranti CK, and Brugge JS. Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol 2002; 4:E83–E90.PubMedCrossRefGoogle Scholar
  32. 32.
    Moser M, Legate KR, Zent R, and Fassler R. The tail of integrins, talin, and kindlins. Science 2009; 324:895–899.PubMedCrossRefGoogle Scholar
  33. 33.
    Roman J, and McDonald JA. Fibronectins and fibronectin receptors in lung development, injury and repair. In: Crystal RG, editor. The lung, 2nd ed. Philadelphia: Lippincott – Raven Publishers; 1997, pp. 737–755.Google Scholar
  34. 34.
    Roman J. Extracellular matrices in lung injury and repair. In: Schwarz M, King T, editor. Interstitial lung disease, 4th ed. London: B.C. Decker, Inc.; 2003, pp. 276–299.Google Scholar
  35. 35.
    Schlaepfer DD, Hauck CR, and Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol 1999; 71:435–478.PubMedCrossRefGoogle Scholar
  36. 36.
    Sheppard D. Functions of pulmonary epithelial integrins: from development to disease. Physiol Rev 2003; 83:673–686.PubMedGoogle Scholar
  37. 37.
    Evans R, Patzak I, Svensson L, De Filippo K, Jones K, McDowall A, and Hogg N. Integrins in immunity. J Cell Sci 2009; 122:215–225.PubMedCrossRefGoogle Scholar
  38. 38.
    Boles BK, Ritzenthaler J, Birkenmeier T, and Roman J. Phorbol ester-induced u-937 differentiation: effects on integrin alpha(5) gene transcription. Am J Physiol Lung Cell Mol Physiol 2000; 278:L703–L712.PubMedGoogle Scholar
  39. 39.
    Prockop DJ. Repair of tissues by adult stem/progenitor cells (mscs): controversies, myths, and changing paradigms. Mol Ther 2009; 17:939–946.PubMedCrossRefGoogle Scholar
  40. 40.
    Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 2000; 287:1442–1446.PubMedCrossRefGoogle Scholar
  41. 41.
    D’Amour K, and Gage FH. New tools for human developmental biology. Nat Biotechnol 2000; 18:381–382.PubMedCrossRefGoogle Scholar
  42. 42.
    Poulsom R, Alison MR, Forbes SJ, and Wright NA. Adult stem cell plasticity. J Pathol 2002; 197:441–456.PubMedCrossRefGoogle Scholar
  43. 43.
    Stripp BR. Hierarchical organization of lung progenitor cells: is there an adult lung tissue stem cell? Proc Am Thorac Soc 2008; 5:695–698.PubMedCrossRefGoogle Scholar
  44. 44.
    Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007; 449:1003–1007.PubMedCrossRefGoogle Scholar
  45. 45.
    Jackson EL, and Alvarez-Buylla A. Characterization of adult neural stem cells and their relation to brain tumors. Cells Tissues Organs 2008; 188:212–224.PubMedCrossRefGoogle Scholar
  46. 46.
    Gopinath SD, and Rando TA. Stem cell review series: aging of the skeletal muscle stem cell niche. Aging Cell 2008; 7:590–598.PubMedCrossRefGoogle Scholar
  47. 47.
    Stripp BR, and Reynolds SD. Maintenance and repair of the bronchiolar epithelium. Proc Am Thorac Soc 2008; 5:328–333.PubMedCrossRefGoogle Scholar
  48. 48.
    Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M, Yajima N, Hamada K, Horie Y, Kubo H et al. Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice. J Clin Invest 2007; 117:2929–2940.PubMedCrossRefGoogle Scholar
  49. 49.
    Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, and Fine A. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 2001; 128:5181–5188.PubMedGoogle Scholar
  50. 50.
    Conget PA, and Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999; 181:67–73.PubMedCrossRefGoogle Scholar
  51. 51.
    Bianco P, Riminucci M, Majolagbe A, Kuznetsov SA, Collins MT, Mankani MH, Corsi A, Bone HG, Wientroub S, Spiegel AM et al. Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone. J Bone Miner Res 2000; 15:120–128.PubMedCrossRefGoogle Scholar
  52. 52.
    Verfaillie CM. Adult stem cells: assessing the case for pluripotency. Trends Cell Biol 2002; 12:502–508.PubMedCrossRefGoogle Scholar
  53. 53.
    Weiss DJ, Kolls JK, Ortiz LA, Panoskaltsis-Mortari A, and Prockop DJ. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc 2008; 5:637–667.PubMedCrossRefGoogle Scholar
  54. 54.
    Daley WP, Peters SB, and Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci 2008; 121:255–264.PubMedCrossRefGoogle Scholar
  55. 55.
    Wilson A, and Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 2006; 6:93–106.PubMedCrossRefGoogle Scholar
  56. 56.
    Coulombel L, Auffray I, Gaugler MH, and Rosemblatt M. Expression and function of integrins on hematopoietic progenitor cells. Acta Haematol 1997; 97:13–21.PubMedCrossRefGoogle Scholar
  57. 57.
    Verfaillie CM, Hurley R, Lundell BI, Zhao C, and Bhatia R. Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors? Acta Haematol 1997; 97:40–52.PubMedCrossRefGoogle Scholar
  58. 58.
    Ali NN, Edgar AJ, Samadikuchaksaraei A, Timson CM, Romanska HM, Polak JM, and Bishop AE. Derivation of type ii alveolar epithelial cells from murine embryonic stem cells. Tissue Eng 2002; 8:541–550.PubMedCrossRefGoogle Scholar
  59. 59.
    Rippon HJ, Polak JM, Qin M, and Bishop AE. Derivation of distal lung epithelial progenitors from murine embryonic stem cells using a novel three-step differentiation protocol. Stem Cells 2006; 24:1389–1398.PubMedCrossRefGoogle Scholar
  60. 60.
    Samadikuchaksaraei A, Cohen S, Isaac K, Rippon HJ, Polak JM, Bielby RC, and Bishop AE. Derivation of distal airway epithelium from human embryonic stem cells. Tissue Eng 2006; 12:867–875.PubMedCrossRefGoogle Scholar
  61. 61.
    Wang D, Haviland DL, Burns AR, Zsigmond E, and Wetsel RA. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 2007; 104:4449–4454.PubMedCrossRefGoogle Scholar
  62. 62.
    Coraux C, Nawrocki-Raby B, Hinnrasky J, Kileztky C, Gaillard D, Dani C, and Puchelle E. Embryonic stem cells generate airway epithelial tissue. Am J Respir Cell Mol Biol 2005; 32:87–92.PubMedCrossRefGoogle Scholar
  63. 63.
    Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, and Carpenter MK. Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol 2001; 19:971–974.PubMedCrossRefGoogle Scholar
  64. 64.
    Evseenko D, Schenke-Layland K, Dravid G, Zhu Y, Hao QL, Scholes J, Chao X, Maclellan WR, and Crooks GM. Identification of the critical extracellular matrix proteins that promote human embryonic stem cell assembly. Stem Cells Dev 2008.Google Scholar
  65. 65.
    Takagi J, Yang Y, Liu JH, Wang JH, and Springer TA. Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface. Nature 2003; 424:969–974.PubMedCrossRefGoogle Scholar
  66. 66.
    Docheva D, Popov C, Mutschler W, and Schieker M. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med 2007; 11:21–38.PubMedCrossRefGoogle Scholar
  67. 67.
    Goessler UR, Bugert P, Bieback K, Stern-Straeter J, Bran G, Sadick H, Hormann K, and Riedel F. In vitro-analysis of integrin-expression in stem-cells from bone marrow and cord blood during chondrogenic differentiation. J Cell Mol Med 2008.Google Scholar
  68. 68.
    Meyers VE, Zayzafoon M, Gonda SR, Gathings WE, and McDonald JM. Modeled microgravity disrupts collagen i/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. J Cell Biochem 2004; 93:697–707.PubMedCrossRefGoogle Scholar
  69. 69.
    Salasznyk RM, Klees RF, Boskey A, and Plopper GE. Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5. J Cell Biochem 2007; 100:499–514.PubMedCrossRefGoogle Scholar
  70. 70.
    Warburton D, Perin L, Defilippo R, Bellusci S, Shi W, and Driscoll B. Stem/progenitor cells in lung development, injury repair, and regeneration. Proc Am Thorac Soc 2008; 5:703–706.PubMedCrossRefGoogle Scholar
  71. 71.
    Boyden EA. Development and growth of the airways. In: WA Hodson, editor. Development of the lung. New York, NY: Marcel Decker; 1977, pp. 3–35.Google Scholar
  72. 72.
    Mollard R, and Dziadek MA. Correlation between epithelial proliferation rates, basement membrane component localization patterns, and morphogenetic potential in the embryonic mouse lung. Am J Respir Cell Mol Biol 1998; 19:71–82.PubMedGoogle Scholar
  73. 73.
    Chen JM, and Little CD. Cellular events associated with lung branching morphogenesis including the deposition of collagen type IV. Dev Biol 1987; 120:311–321.PubMedCrossRefGoogle Scholar
  74. 74.
    Ekblom P, Ekblom M, Fecker L, Klein G, Zhang HY, Kadoya Y, Chu ML, Mayer U, and Timpl R. Role of mesenchymal nidogen for epithelial morphogenesis in vitro. Development 1994; 120:2003–2014.PubMedGoogle Scholar
  75. 75.
    Larsen M, Wei C, and Yamada KM. Cell and fibronectin dynamics during branching morphogenesis. J Cell Sci 2006; 119:3376–3384.PubMedCrossRefGoogle Scholar
  76. 76.
    Roman J, Little CW, and McDonald JA. Potential role of RGD-binding integrins in mammalian lung branching morphogenesis. Development 1991; 112:551–558.PubMedGoogle Scholar
  77. 77.
    Ma W, Tavakoli T, Derby E, Serebryakova Y, Rao MS, and Mattson MP. Cell-extracellular matrix interactions regulate neural differentiation of human embryonic stem cells. BMC Dev Biol 2008; 8:90.PubMedCrossRefGoogle Scholar
  78. 78.
    Tate CC, Shear DA, Tate MC, Archer DR, Stein DG, and LaPlaca MC. Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J Tissue Eng Regen Med 2009; 3:208–217.PubMedCrossRefGoogle Scholar
  79. 79.
    Chastain SR, Kundu AK, Dhar S, Calvert JW, and Putnam AJ. Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation. J Biomed Mater Res A 2006; 78:73–85.PubMedGoogle Scholar
  80. 80.
    Omori K, Tada Y, Suzuki T, Nomoto Y, Matsuzuka T, Kobayashi K, Nakamura T, Kanemaru S, Yamashita M, and Asato R. Clinical application of in situ tissue engineering using a scaffolding technique for reconstruction of the larynx and trachea. Ann Otol Rhinol Laryngol 2008; 117:673–678.PubMedGoogle Scholar
  81. 81.
    Urita Y, Komuro H, Chen G, Shinya M, Saihara R, and Kaneko M. Evaluation of diaphragmatic hernia repair using plga mesh-collagen sponge hybrid scaffold: an experimental study in a rat model. Pediatr Surg Int 2008; 24:1041–1045.PubMedCrossRefGoogle Scholar
  82. 82.
    Sato T, and Nakamura T. Tissue-engineered airway replacement. Lancet 2008; 372:2003–2004.PubMedCrossRefGoogle Scholar
  83. 83.
    Sato T, Tao H, Araki M, Ueda H, Omori K, and Nakamura T. Replacement of the left main bronchus with a tissue-engineered prosthesis in a canine model. Ann Thorac Surg 2008; 86:422–428.PubMedCrossRefGoogle Scholar
  84. 84.
    Andrade CF, Wong AP, Waddell TK, Keshavjee S, and Liu M. Cell-based tissue engineering for lung regeneration. Am J Physiol Lung Cell Mol Physiol 2007; 292:L510–L518.PubMedCrossRefGoogle Scholar
  85. 85.
    Tomei AA, Boschetti F, Gervaso F, and Swartz MA. 3D collagen cultures under well-defined dynamic strain: a novel strain device with a porous elastomeric support. Biotechnol Bioeng 2009; 103(1):217–225.PubMedCrossRefGoogle Scholar
  86. 86.
    Mondrinos MJ, Koutzaki SH, Poblete HM, Crisanti MC, Lelkes PI, and Finck CM. In vivo pulmonary tissue engineering: contribution of donor-derived endothelial cells to construct vascularization. Tissue Eng Part A 2008; 14:361–368.PubMedCrossRefGoogle Scholar
  87. 87.
    Giancotti FG, and Tarone G. Positional control of cell fate through joint integrin/receptor protein kinase signaling. Annu Rev Cell Dev Biol 2003; 19:173–206.PubMedCrossRefGoogle Scholar
  88. 88.
    Plantefaber LC, and Hynes RO. Changes in integrin receptors on oncogenically transformed cells. Cell 1989; 56:281–290.PubMedCrossRefGoogle Scholar
  89. 89.
    Guo W, Pylayeva Y, Pepe A, Yoshioka T, Muller WJ, Inghirami G, and Giancotti FG. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 2006; 126:489–502.PubMedCrossRefGoogle Scholar
  90. 90.
    Pontier SM, and Muller WJ. Integrins in mammary-stem-cell biology and breast-cancer progression – a role in cancer stem cells? J Cell Sci 2009; 122:207–214.PubMedCrossRefGoogle Scholar
  91. 91.
    Iwasaki H, and Suda T. Cancer stem cells and their niche. Cancer Sci 2009; 100:1166–1172.PubMedCrossRefGoogle Scholar
  92. 92.
    Ritzenthaler JD, Han S, and Roman J. Stimulation of lung carcinoma cell growth by fibronectin-integrin signalling. Mol Biosyst 2008; 4:1160–1169.PubMedCrossRefGoogle Scholar
  93. 93.
    Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, and Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005; 33:145–152.PubMedCrossRefGoogle Scholar
  94. 94.
    Strieter RM, Keeley EC, Hughes MA, Burdick MD, and Mehrad B. The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis. J Leukoc Biol 2009.Google Scholar
  95. 95.
    Ganter MT, Roux J, Miyazawa B, Howard M, Frank JA, Su G, Sheppard D, Violette SM, Weinreb PH, Horan GS et al. Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circ Res 2008; 102:804–812.PubMedCrossRefGoogle Scholar
  96. 96.
    Koval M, Ward C, Findley MK, Roser-Page S, Helms MN, and Roman J. Extracellular matrix influences alveolar epithelial claudin expression and barrier function. Am J Respir Cell Mol Biol 2010; 42(2):172–180.PubMedCrossRefGoogle Scholar
  97. 97.
    Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, and Jacks T. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005; 121:823–835.PubMedCrossRefGoogle Scholar
  98. 98.
    George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, and Hynes RO. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 1993; 119:1079–1091.PubMedGoogle Scholar
  99. 99.
    George EL, Baldwin HS, and Hynes RO. Fibronectins are essential for heart and blood vessel morphogenesis but are dispensable for initial specification of precursor cells. Blood 1997; 90:3073–3081.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of Pulmonary, Allergy and Critical Care Medicine, Department of MedicineEmory University School of MedicineAtlantaUSA
  2. 2.Department of MedicineUniversity of Louisville Health Sciences CenterLouisvilleUSA

Personalised recommendations