In vitro models to study human lung development, disease and homeostasis

Physiology

Volumn 32, Issue 3, 2017, Pages 246-260

  Miller, Alyssa J ^a   Spence, Jason R ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL; BIOLOGICAL MODEL; CELL CULTURE TECHNIQUE; CELL LINE; DISEASE MODEL; GROWTH, DEVELOPMENT AND AGING; HOMEOSTASIS; HUMAN; IN VITRO STUDY; LUNG; LUNG DISEASE; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; PLURIPOTENT STEM CELL; PROCEDURES; REGENERATION; TRENDS;

ANIMALS; CELL CULTURE TECHNIQUES; CELL LINE; DISEASE MODELS, ANIMAL; HOMEOSTASIS; HUMANS; IN VITRO TECHNIQUES; LUNG; LUNG DISEASES; MODELS, BIOLOGICAL; PLURIPOTENT STEM CELLS; REGENERATION;

EID: 85018807540     PISSN: 15489213     EISSN: 15489221     Source Type: Journal    
DOI: 10.1152/physiol.00041.2016     Document Type: Review

References (178)

1. El Agha E, Moiseenko A, Kheirollahi V, De Langhe S, Crnkovic S, Kwapiszewska G, Kosanovic D, Schwind F, Schermuly RT, Henneke I, MacKenzie B, Quantius J, Herold S, Ntokou A, Ahlbrecht K, Morty RE, Günther A, Seeger W, Bellusci S. Two-way conversion between lipogenic and myogenic fibroblastic phenotypes marks the progression and resolution of lung fibrosis. Cell Stem Cell 20: 261-273.e3, 2017. doi:10.1016/j.stem.2016.10.004.
2. Alvarado A, Arce I. Metabolic functions of the lung, disorders and associated pathologies. J Clin Med Res 8: 689-700, 2016. doi:10.14740/jocmr2668w.
3. Andrade CF, Wong AP, Waddell TK, Keshavjee S, Liu M. Cell-based tissue engineering for lung regeneration. Am J Physiol Lung Cell Mol Physiol 292: L510-L518, 2007. doi:10.1152/ajplung.00175.2006.
4. Aurora M, Spence JR. hPSC-derived lung and intestinal organoids as models of human fetal tissue. Dev Biol 420: 230-238, 2016. doi:10.1016/j.ydbio.2016.06.006.
5. Balestrini JL, Gard AL, Gerhold KA, Wilcox EC, Liu A, Schwan J, Le AV, Baevova P, Dimitrievska S, Zhao L, Sundaram S, Sun H, Rittié L, Dyal R, Broekelmann TJ, Mecham RP, Schwartz MA, Niklason LE, White ES. Comparative biology of decellularized lung matrix: implications of species mismatch in regenerative medicine. Biomaterials 102: 220-230, 2016. doi:10.1016/j.biomaterials.2016.06.025.
6. Bals R, Beisswenger C, Blouquit S, Chinet T. Isolation and air-liquid interface culture of human large airway and bronchiolar epithelial cells. J Cyst Fibros 3, Suppl 2: 49-51, 2004. doi:10.1016/j.jcf.2004.05.010.
7. Barkauskas CE, Cronce MJ, Rackley CR, Bowie EJ, Keene DR, Stripp BR, Randell SH, Noble PW, Hogan BLM. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 123: 3025-3036, 2013. doi:10.1172/JCI68782.
8. Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 22: 672-688, 2003. doi:10.1183/09031936.03.00040703.
9. Bateman ED, Turner-Warwick M, Adelmann-Grill BC. Immunohistochemical study of collagen types in human foetal lung and fibrotic lung disease. Thorax 36: 645-653, 1981. doi:10.1136/thx.36.9.645.
10. Beers MF, Morrisey EE. The three R’s of lung health and disease: repair, remodeling, and regeneration. J Clin Invest 121: 2065-2073, 2011. doi:10.1172/JCI45961.
11. Benam KH, Villenave R, Lucchesi C, Varone A, Hubeau C, Lee H-H, Alves SE, Salmon M, Ferrante TC, Weaver JC, Bahinski A, Hamilton GA, Ingber DE. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods 13: 151-157, 2016. doi:10.1038/nmeth.3697.
12. Bernacki SH, Nelson AL, Abdullah L, Sheehan JK, Harris A, Davis CW, Randell SH. Mucin gene expression during differentiation of human airway epithelia in vitro. Muc4 and muc5b are strongly induced. Am J Respir Cell Mol Biol 20: 595-604, 1999. doi:10.1165/ajrcmb.20.4.3442.
13. Bernhard W. Lung surfactant: function and composition in the context of development and respiratory physiology. Ann Anat 208: 146-150, 2016. doi:10.1016/j.aanat.2016.08.003.
14. Bhatt AJ, Pryhuber GS, Huyck H, Watkins RH, Metlay LA, Maniscalco WM. Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia. Am J Respir Crit Care Med 164: 1971-1980, 2001. doi:10.1164/ajrccm.164.10.2101140.
15. Boers JE, Ambergen AW, Thunnissen FB. Number and proliferation of clara cells in normal human airway epithelium. Am J Respir Crit Care Med 159: 1585-1591, 1999. doi:10.1164/ajrccm.159.5.9806044.
16. Boers JE, den Brok JL, Koudstaal J, Arends JW, Thunnissen FB. Number and proliferation of neuroendocrine cells in normal human airway epithelium. Am J Respir Crit Care Med 154: 758-763, 1996. doi:10.1164/ajrccm.154.3.8810616.
17. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15: 786-801, 2014. doi:10.1038/nrm3904.
18. Bonvillain RW, Danchuk S, Sullivan DE, Betancourt AM, Semon JA, Eagle ME, Mayeux JP, Gregory AN, Wang G, Townley IK, Borg ZD, Weiss DJ, Bunnell BA. A nonhuman primate model of lung regeneration: detergent-mediated decellularization and initial in vitro recellularization with mesenchymal stem cells. Tissue Eng Part A 18: 2437-2452, 2012. doi:10.1089/ten.tea.2011.0594.
19. Booth AJ, Hadley R, Cornett AM, Dreffs AA, Matthes SA, Tsui JL, Weiss K, Horowitz JC, Fiore VF, Barker TH, Moore BB, Martinez FJ, Niklason LE, White ES. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am J Respir Crit Care Med 186: 866-876, 2012. doi:10.1164/rccm.201204-0754OC.
20. Bower DV, Lee H-K, Lansford R, Zinn K, Warburton D, Fraser SE, Jesudason EC. Airway branching has conserved needs for local parasympathetic innervation but not neurotransmission. BMC Biol 12: 92, 2014. doi:10.1186/s12915-014-0092-2.
21. Branchfield K, Li R, Lungova V, Verheyden JM, McCulley D, Sun X. A three-dimensional study of alveologenesis in mouse lung. Dev Biol 409: 429-441, 2016. doi:10.1016/j.ydbio.2015.11.017.
22. Branchfield K, Nantie L, Verheyden JM, Sui P, Wienhold MD, Sun X. Pulmonary neuroendocrine cells function as airway sensors to control lung immune response. Science 351: 707-710, 2016. doi:10.1126/science.aad7969.
23. Brune KA, Ferreira F, Mandke P, Chau E, Aggarwal NR, D’Alessio FR, Lambert AA, Kirk G, Blankson J, Drummond MB, Tsibris AM, Sidhaye VK. HIV impairs lung epithelial integrity and enters the epithelium to promote chronic lung inflammation. PLoS One 11: e0149679, 2016. doi:10.1371/journal.pone.0149679.
24. Burns AJ, Delalande J-MM, Le Douarin NM. In ovo transplantation of enteric nervous system precursors from vagal to sacral neural crest results in extensive hindgut colonisation. Development 129: 2785-2796, 2002.
25. Camp JG, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Bräuninger M, Lewitus E, Sykes A, Hevers W, Lancaster M, Knoblich JA, Lachmann R, Pääbo S, Huttner WB, Treutlein B. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci USA 112: 15672-15677, 2015. doi:10.1073/pnas.1520760112.
26. Cardoso WV. Molecular regulation of lung development. Annu Rev Physiol 63: 471-494, 2001. doi:10.1146/annurev.physiol.63.1.471.
27. Chang DR, Martinez Alanis D, Miller RK, Ji H, Akiyama H, McCrea PD, Chen J. Lung epithelial branching program antagonizes alveolar differentiation. Proc Natl Acad Sci USA 110: 18042-18051, 2013. doi:10.1073/pnas.1311760110.
28. Chao C-M, Moiseenko A, Zimmer K-P, Bellusci S. Alveologenesis: key cellular players and fibroblast growth factor 10 signaling. Mol Cell Pediatr 3: 17, 2016. doi:10.1186/s40348-016-0045-7.
29. Chen L, Acciani T, Le Cras T, Lutzko C, Perl A-KT. Dynamic regulation of platelet-derived growth factor receptor _ expression in alveolar fibroblasts during realveolarization. Am J Respir Cell Mol Biol 47: 517-527, 2012. doi:10.1165/rcmb.2012-0030OC.
30. Cortiella J, Nichols JE, Kojima K, Bonassar LJ, Dargon P, Roy AK, Vacant MP, Niles JA, Vacanti CA. Tissue-engineered lung: an in vivo and in vitro comparison of polyglycolic acid and pluronic F-127 hydrogel/somatic lung progenitor cell constructs to support tissue growth. Tissue Eng 12: 1213-1225, 2006. doi:10.1089/ten.2006.12.1213.
31. Crane AM, Kramer P, Bui JH, Chung WJ, Li XS, Gonzalez-Garay ML, Hawkins F, Liao W, Mora D, Choi S, Wang J, Sun HC, Paschon DE, Guschin DY, Gregory PD, Kotton DN, Holmes MC, Sorscher EJ, Davis BR. Targeted correction and restored function of the CFTR gene in cystic fibrosis induced pluripotent stem cells. Stem Cell Reports 4: 569-577, 2015. doi:10.1016/j.stemcr.2015.02.005.
32. Creager HM, Zeng H, Pulit-Penaloza JA, Maines TR, Tumpey TM, Belser JA. In vitro exposure system for study of aerosolized influenza virus. Virology 500: 62-70, 2017. doi:10.1016/j.virol.2016.10.007.
33. Cutting GR. Cystic fibrosis genetics: from molecular understanding to clinical application. Nat Rev Genet 16: 45-56, 2015. doi:10.1038/nrg3849.
34. Cutz E, Perrin DG, Pan J, Haas EA, Krous HF. Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction. Pediatr Dev Pathol 10: 106-116, 2007. doi:10.2350/06-06-0113.1.
35. D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23: 1534-1541, 2005. doi:10.1038/nbt1163.
36. Danahay H, Pessotti AD, Coote J, Montgomery BE, Xia D, Wilson A, Yang H, Wang Z, Bevan L, Thomas C, Petit S, London A, LeMotte P, Doelemeyer A, Vélez-Reyes GL, Bernasconi P, Fryer CJ, Edwards M, Capodieci P, Chen A, Hild M, Jaffe AB. Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung. Cell Reports 10: 239-252, 2015. doi:10.1016/j.celrep.2014.12.017.
37. Davis PB, Yasothan U, Kirkpatrick P. Ivacaftor. Nat Rev Drug Discov 11: 349-350, 2012. doi:10.1038/nrd3723.
38. de Bakker BS, de Jong KH, Hagoort J, de Bree K, Besselink CT, de Kanter FEC, Veldhuis T, Bais B, Schildmeijer R, Ruijter JM, Oostra R-J, Christoffels VM, Moorman AFM. An interactive three-dimensional digital atlas and quantitative database of human development. Science 354: aag0053, 2016. doi:10.1126/science.aag0053.
39. Desai TJ, Brownfield DG, Krasnow MA. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 507: 190-194, 2014. doi:10.1038/nature12930.
40. Domyan ET, Sun X. Patterning and plasticity in development of the respiratory lineage. Dev Dyn 240: 477-485, 2011. doi:10.1002/dvdy.22504.
41. Dye BR, Dedhia PH, Miller AJ, Nagy MS, White ES, Shea LD, Spence JR. A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. eLife 5: e19732, 2016. doi:10.7554/eLife.19732.
42. Dye BR, Hill DR, Ferguson MA, Tsai Y-H, Nagy MS, Dyal R, Wells JM, Mayhew CN, Nattiv R, Klein OD, White ES, Deutsch GH, Spence JR. In vitro generation of human pluripotent stem cell derived lung organoids. eLife 4: e05098, 2015. doi:10.7554/eLife.05098.
43. Dye BR, Miller AJ, Spence JR. How to Grow a Lung: Applying Principles of Developmental Biology to Generate Lung Lineages from Human Pluripotent Stem Cells. Curr Pathobiol Rep 4: 47-57, 2016. doi:10.1007/s40139-016-0102-x.
44. Ebina M, Takahashi T, Chiba T, Motomiya M. Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study. Am Rev Respir Dis 148: 720-726, 1993. doi:10.1164/ajrccm/148.3.720.
45. Finkbeiner SR, Freeman JJ, Wieck MM, El-Nachef W, Altheim CH, Tsai Y-H, Huang S, Dyal R, White ES, Grikscheit TC, Teitelbaum DH, Spence JR. Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. Biol Open 4: 1462-1472, 2015. doi:10.1242/bio.013235.
46. Finkbeiner SR, Hill DR, Altheim CH, Dedhia PH, Taylor MJ, Tsai Y-H, Chin AM, Mahe MM, Watson CL, Freeman JJ, Nattiv R, Thomson M, Klein OD, Shroyer NF, Helmrath MA, Teitelbaum DH, Dempsey PJ, Spence JR. Transcriptome-wide analysis reveals hallmarks of human intestine development and maturation in vitro and in vivo. Stem Cell Reports 4: 1140-1155, 2015. doi:10.1016/j.stemcr.2015.04.010.
47. Firth AL, Menon T, Parker GS, Qualls SJ, Lewis BM, Ke E, Dargitz CT, Wright R, Khanna A, Gage FH, Verma IM. Functional gene correction for cystic fibrosis in lung epithelial cells generated from patient iPSCs. Cell Reports 12: 1385-1390, 2015. doi:10.1016/j.celrep.2015.07.062.
48. Franzdóttir SR, Axelsson IT, Arason AJ, Baldursson O, Gudjonsson T, Magnusson MK. Airway branching morphogenesis in three dimensional culture. Respir Res 11: 162, 2010. doi:10.1186/1465-9921-11-162.
49. Freem LJ, Escot S, Tannahill D, Druckenbrod NR, Thapar N, Burns AJ. The intrinsic innervation of the lung is derived from neural crest cells as shown by optical projection tomography in Wnt1-Cre;YFP reporter mice. J Anat 217: 651-664, 2010. doi:10.1111/j.1469-7580.2010.01295.x.
50. Fulcher ML, Gabriel SE, Olsen JC, Tatreau JR, Gentzsch M, Livanos E, Saavedra MT, Salmon P, Randell SH. Novel human bronchial epithelial cell lines for cystic fibrosis research. Am J Physiol Lung Cell Mol Physiol 296: L82-L91, 2009. doi:10.1152/ajplung.90314.2008.
51. Fulcher ML, Randell SH. Human nasal and tracheo-bronchial respiratory epithelial cell culture. Methods Mol Biol 945: 109-121, 2013. doi:10.1007/978-1-62703-125-7_8.
52. Ghaedi M, Calle EA, Mendez JJ, Gard AL, Balestrini J, Booth A, Bove PF, Gui L, White ES, Niklason LE. Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix. J Clin Invest 123: 4950-4962, 2013. doi:10.1172/JCI68793.
53. Ghaedi M, Mendez JJ, Bove PF, Sivarapatna A, Raredon MSB, Niklason LE. Alveolar epithelial differentiation of human induced pluripotent stem cells in a rotating bioreactor. Biomaterials 35: 699-710, 2014. doi:10.1016/j.biomaterials.2013.10.018.
54. Ghaedi M, Niklason LE, Williams J. Development of lung epithelium from induced pluripotent stem cells. Curr Transplant Rep 2: 81-89, 2015. doi:10.1007/s40472-014-0039-0.
55. Gilpin SE, Charest JM, Ren X, Ott HC. Bioengineering lungs for transplantation. Thorac Surg Clin 26: 163-171, 2016. doi:10.1016/j.thorsurg.2015.12.004.
56. Gilpin SE, Ott HC. Using nature’s platform to engineer bio-artificial lungs. Ann Am Thorac Soc 12, Suppl 1: S45-S49, 2015. doi:10.1513/AnnalsATS.201408-366MG.
57. Gilpin SE, Ren X, Okamoto T, Guyette JP, Mou H, Rajagopal J, Mathisen DJ, Vacanti JP, Ott HC. Enhanced lung epithelial specification of human induced pluripotent stem cells on decellularized lung matrix. Ann Thorac Surg 98: 1721-1729, 2014.
58. Gjorevski N, Sachs N, Manfrin A, Giger S, Bragina ME, Ordóñez-Morán P, Clevers H, Lutolf MP. Designer matrices for intestinal stem cell and organoid culture. Nature 539: 560-564, 2016. doi:10.1038/nature20168.
59. Glasser SW, Hagood JS, Wong S, Taype CA, Madala SK, Hardie WD. Mechanisms of lung fibrosis resolution. Am J Pathol 186: 1066-1077, 2016. doi:10.1016/j.ajpath.2016.01.018.
60. Gonzalez RF, Allen L, Gonzales L, Ballard PL, Dobbs LG. HTII-280, a biomarker specific to the apical plasma membrane of human lung alveolar type II cells. J Histochem Cytochem 58: 891-901, 2010. doi:10.1369/jhc.2010.956433.
61. Gotoh S, Ito I, Nagasaki T, Yamamoto Y, Konishi S, Korogi Y, Matsumoto H, Muro S, Hirai T, Funato M, Mae S, Toyoda T, Sato-Otsubo A, Ogawa S, Osafune K, Mishima M. Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells. Stem Cell Reports 3: 394-403, 2014. doi:10.1016/j.stemcr.2014.07.005.
62. Green J, Endale M, Auer H, Perl AK. Diversity of interstitial lung fibroblasts is regulated by platelet-derived growth factor receptor _ kinase activity. Am J Respir Cell Mol Biol 54: 532-545, 2016. doi:10.1165/rcmb.2015-0095OC.
63. Green MD, Chen A, Nostro M-C, d’Souza SL, Schaniel C, Lemischka IR, Gouon-Evans V, Keller G, Snoeck H-W. Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nat Biotechnol 29: 267-272, 2011. doi:10.1038/nbt.1788.
64. Gruenert DC, Willems M, Cassiman JJ, Frizzell RA. Established cell lines used in cystic fibrosis research. J Cyst Fibros 3, Suppl 2: 191-196, 2004. doi:10.1016/j.jcf.2004.05.040.
65. Gu X, Karp PH, Brody SL, Pierce RA, Welsh MJ, Holtzman MJ, Ben-Shahar Y. Chemosensory functions for pulmonary neuroendocrine cells. Am J Respir Cell Mol Biol 50: 637-646, 2014. doi:10.1165/rcmb.2013-0199OC.
66. Guyette JP, Gilpin SE, Charest JM, Tapias LF, Ren X, Ott HC. Perfusion decellularization of whole organs. Nat Protoc 9: 1451-1468, 2014. doi:10.1038/nprot.2014.097.
67. Hackett T-L, Shaheen F, Johnson A, Wadsworth S, Pechkovsky DV, Jacoby DB, Kicic A, Stick SM, Knight DA. Characterization of side population cells from human airway epithelium. Stem Cells 26: 2576-2585, 2008. doi:10.1634/stemcells.2008-0171.
68. Han RNN, Babaei S, Robb M, Lee T, Ridsdale R, Ackerley C, Post M, Stewart DJ. Defective lung vascular development and fatal respiratory distress in endothelial NO synthase-deficient mice: a model of alveolar capillary dysplasia? Circ Res 94: 1115-1123, 2004. doi:10.1161/01. RES.0000125624.85852.1E.
69. Hannan NRF, Fordham RP, Syed YA, Moignard V, Berry A, Bautista R, Hanley NA, Jensen KB, Vallier L. Generation of multipotent foregut stem cells from human pluripotent stem cells. Stem Cell Reports 1: 293-306, 2013. doi:10.1016/j.stemcr.2013.09.003.
70. Hannan NRF, Sampaziotis F, Segeritz C-P, Hanley NA, Vallier L. Generation of distal airway epithelium from multipotent human foregut stem cells. Stem Cells Dev 24: 1680-1690, 2015. doi:10.1089/scd.2014.0512.
71. Harunaga JS, Doyle AD, Yamada KM. Local and global dynamics of the basement membrane during branching morphogenesis require protease activity and actomyosin contractility. Dev Biol 394: 197-205, 2014. doi:10.1016/j.ydbio.2014.08.014.
72. Haworth SG, Hislop AA. Lung development-the effects of chronic hypoxia. Semin Neonatol 8: 1-8, 2003. doi:10.1016/S1084-2756(02)00195-1.
73. Hegab AE, Arai D, Gao J, Kuroda A, Yasuda H, Ishii M, Naoki K, Soejima K, Betsuyaku T. Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior. Stem Cell Res (Amst) 15: 109-121, 2015. doi:10.1016/j.scr.2015.05.005.
74. Hermanns MI, Unger RE, Kehe K, Peters K, Kirkpatrick CJ. Lung epithelial cell lines in coculture with human pulmonary microvascular endothelial cells: development of an alveolo-capillary barrier in vitro. Lab Invest 84: 736-752, 2004. doi:10.1038/labinvest.3700081.
75. Herriges M, Morrisey EE. Lung development: orchestrating the generation and regeneration of a complex organ. Development 141: 502-513, 2014. doi:10.1242/dev.098186.
76. Hild M, Jaffe AB. Production of 3-D airway organoids from primary human airway basal cells and their use in high-throughput screening. Curr Protoc Stem Cell Biol 37: IE.9.1.9.15502-IE, 2016. doi:10.1002/cpsc.1.
77. Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, Stoltz DA, Welsh MJ. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science 345: 818-822, 2014. doi:10.1126/science.1255825.
78. Holden VI, Breen P, Houle S, Dozois CM, Bachman MA. Klebsiella pneumoniae Siderophores induce inflammation, bacterial dissemination, and HIF-1_ stabilization during pneumonia. MBio 7: e01397-16, 2016. doi:10.1128/mBio.01397-16.
79. Hong KU, Reynolds SD, Watkins S, Fuchs E, Stripp BR. Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am J Pathol 164: 577-588, 2004. doi:10.1016/S0002-9440(10)63147-1.
80. Hoo AF, Henschen M, Dezateux C, Costeloe K, Stocks J. Respiratory function among preterm infants whose mothers smoked during pregnancy. Am J Respir Crit Care Med 158: 700-705, 1998. doi:10.1164/ajrccm.158.3.9711057.
81. Huang SXL, Islam MN, O’Neill J, Hu Z, Yang Y-G, Chen Y-W, Mumau M, Green MD, Vunjak-Novakovic G, Bhattacharya J, Snoeck H-W. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol 32: 84-91, 2014. doi:10.1038/nbt.2754.
82. Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S, Hamilton GA, Thorneloe KS, McAlexander MA, Ingber DE. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-achip microdevice. Sci Transl Med 4: 159ra147, 2012. doi:10.1126/scitranslmed.3004249.
83. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 328: 1662-1668, 2010. doi:10.1126/science.1188302.
84. Jain R, Barkauskas CE, Takeda N, Bowie EJ, Aghajanian H, Wang Q, Padmanabhan A, Manderfield LJ, Gupta M, Li D, Li L, Trivedi CM, Hogan BLM, Epstein JA. Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung. Nat Commun 6: 6727, 2015. doi:10.1038/ncomms7727.
85. Kim CFB, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121: 823-835, 2005. doi:10.1016/j.cell.2005.03.032.
86. Kim HY, Nelson CM. Extracellular matrix and cytoskeletal dynamics during branching morphogenesis. Organogenesis 8: 56-64, 2012.
87. Kim HY, Pang M-F, Varner VD, Kojima L, Miller E, Radisky DC, Nelson CM. Localized smooth muscle differentiation is essential for epithelial bifurcation during branching morphogenesis of the mammalian lung. Dev Cell 34: 719-726, 2015. doi:10.1016/j.devcel.2015.08.012.
88. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 109: 571-577, 2002. doi:10.1172/JCI0215217.
89. Konishi S, Gotoh S, Tateishi K, Yamamoto Y, Korogi Y, Nagasaki T, Matsumoto H, Muro S, Hirai T, Ito I, Tsukita S, Mishima M. Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells. Stem Cell Reports 6: 18-25, 2016. doi:10.1016/j.stemcr.2015.11.010.
90. Kotton DN, Morrisey EE. Lung regeneration: mechanisms, applications and emerging stem cell populations. Nat Med 20: 822-832, 2014. doi:10.1038/nm.3642.
91. Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D’Amour KA, Carpenter MK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26: 443-452, 2008. doi:10.1038/nbt1393.
92. Lee J-H, Bhang DH, Beede A, Huang TL, Stripp BR, Bloch KD, Wagers AJ, Tseng Y-H, Ryeom S, Kim CF. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 156: 440-455, 2014. doi:10.1016/j.cell.2013.12.039.
93. LeSimple P, Liao J, Robert R, Gruenert DC, Hanrahan JW. Cystic fibrosis transmembrane conductance regulator trafficking modulates the barrier function of airway epithelial cell monolayers. J Physiol 588: 1195-1209, 2010. doi:10.1113/jphysiol.2009.182246.
94. Liu X, Ory V, Chapman S, Yuan H, Albanese C, Kallakury B, Timofeeva OA, Nealon C, Dakic A, Simic V, Haddad BR, Rhim JS, Dritschilo A, Riegel A, McBride A, Schlegel R. ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am J Pathol 180: 599-607, 2012. doi:10.1016/j.ajpath.2011.10.036.
95. Longmire TA, Ikonomou L, Hawkins F, Christodoulou C, Cao Y, Jean JC, Kwok LW, Mou H, Rajagopal J, Shen SS, Dowton AA, Serra M, Weiss DJ, Green MD, Snoeck H-W, Ramirez MI, Kotton DN. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 10: 398-411, 2012. doi:10.1016/j.stem.2012.01.019.
96. Mak IW, Evaniew N, Ghert M. Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res 6: 114-118, 2014.
97. Massaro D, Massaro GD. Invited Review: pulmonary alveoli: formation, the “call for oxygen,” and other regulators. Am J Physiol Lung Cell Mol Physiol 282: L345-L358, 2002. doi:10.1152/ajplung.00374.2001.
98. Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295: L379-L399, 2008. doi:10.1152/ajplung.00010.2008.
99. McCracken KW, Catá EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, Tsai Y-H, Mayhew CN, Spence JR, Zavros Y, Wells JM. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516: 400-404, 2014. doi:10.1038/nature13863.
100. McCracken KW, Howell JC, Wells JM, Spence JR. Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc 6: 1920-1928, 2011. doi:10.1038/nprot.2011.410.
101. McCulley D, Wienhold M, Sun X. The pulmonary mesenchyme directs lung development. Curr Opin Genet Dev 32: 98-105, 2015. doi:10.1016/j.gde.2015.01.011.
102. McGowan SE. Extracellular matrix and the regulation of lung development and repair. FASEB J 6: 2895-2904, 1992.
103. McQualter JL, Bertoncello I. Clonal culture of adult mouse lung epithelial stem/progenitor cells. Methods Mol Biol 1235: 231-241, 2015. doi:10.1007/978-1-4939-1785-3_17.
104. Mercer RR, Russell ML, Roggli VL, Crapo JD. Cell number and distribution in human and rat airways. Am J Respir Cell Mol Biol 10: 613-624, 1994. doi:10.1165/ajrcmb.10.6.8003339.
105. Metzger RJ, Klein OD, Martin GR, Krasnow MA. The branching programme of mouse lung development. Nature 453: 745-750, 2008. doi:10.1038/nature07005.
106. Molina SA, Stauffer B, Moriarty HK, Kim AH, McCarty NA, Koval M. Junctional abnormalities in human airway epithelial cells expressing F508del CFTR. Am J Physiol Lung Cell Mol Physiol 309: L475-L487, 2015. doi:10.1152/ajplung.00060.2015.
107. Mondrinos MJ, Koutzaki S, Lelkes PI, Finck CM. A tissue-engineered model of fetal distal lung tissue. Am J Physiol Lung Cell Mol Physiol 293: L639-L650, 2007. doi:10.1152/ajplung.00403.2006.
108. Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 294: L152-L160, 2008. doi:10.1152/ajplung.00313.2007.
109. Morris GE, Bridge JC, Brace LA, Knox AJ, Aylott JW, Brightling CE, Ghaemmaghami AM, Rose FRAJ. A novel electrospun biphasic scaffold provides optimal three-dimensional topography for in vitro co-culture of airway epithelial and fibroblast cells. Biofabrication 6: 035014, 2014. doi:10.1088/1758-5082/6/3/035014.
110. Morrisey EE, Hogan BLM. Preparing for the first breath: genetic and cellular mechanisms in lung development. Dev Cell 18: 8-23, 2010. doi:10.1016/j.devcel.2009.12.010.
111. Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, Zhang B, Solomon GM, Turner B, Bihler H, Harrington J, Lapey A, Channick C, Keyes C, Freund A, Artandi S, Mense M, Rowe S, Engelhardt JF, Hsu Y-C, Rajagopal J. Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell 19: 217-231, 2016. doi:10.1016/j.stem.2016.05.012.
112. Mou H, Zhao R, Sherwood R, Ahfeldt T, Lapey A, Wain J, Sicilian L, Izvolsky K, Musunuru K, Cowan C, Rajagopal J. Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell Stem Cell 10: 385-397, 2012. doi:10.1016/j.stem.2012.01.018.
113. Myllärniemi M, Kaarteenaho R. Pharmacological treatment of idiopathic pulmonary fibrosis-preclinical and clinical studies of pirfenidone, nintedanib, and N-acetylcysteine. Eur Clin Respir J 2: 26385, 2015. doi:10.3402/ecrj.v2.26385.
114. Enemchukwu NO, Cruz-Acuña R, Bongiorno T, Johnson CT, García JR, Sulchek T, García AJ. Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis. J Cell Biol 212: 113-124, 2016. doi:10.1083/jcb.201506055.
115. Neuberger T, Burton B, Clark H, Van Goor F. Use of primary cultures of human bronchial epithelial cells isolated from cystic fibrosis patients for the pre-clinical testing of CFTR modulators. Methods Mol Biol 741: 39-54, 2011. doi:10.1007/978-1-61779-117-8_4.
116. O’Leary C, Cavanagh B, Unger RE, Kirkpatrick CJ, O’Dea S, O’Brien FJ, Cryan S-A. The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold. Biomaterials 85: 111-127, 2016. doi:10.1016/j.biomaterials.2016.01.065.
117. Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, Kotton D, Vacanti JP. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med 16: 927-933, 2010. doi:10.1038/nm.2193.
118. Pageau SC, Sazonova OV, Wong JY, Soto AM, Sonnenschein C. The effect of stromal components on the modulation of the phenotype of human bronchial epithelial cells in 3D culture. Biomaterials 32: 7169-7180, 2011. doi:10.1016/j.biomaterials.2011.06.017.
119. Pardo-Saganta A, Law BM, Gonzalez-Celeiro M, Vinarsky V, Rajagopal J. Ciliated cells of pseudostratified airway epithelium do not become mucous cells after ovalbumin challenge. Am J Respir Cell Mol Biol 48: 364-373, 2013. doi:10.1165/rcmb.2012-0146OC.
120. Pardo-Saganta A, Law BM, Tata PR, Villoria J, Saez B, Mou H, Zhao R, Rajagopal J. Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations. Cell Stem Cell 16: 184-197, 2015. doi:10.1016/j.stem.2015.01.002.
121. Patel VN, Pineda DL, Hoffman MP. The function of heparan sulfate during branching morphogenesis. Matrix Biol 57-58: 311-323, 2017. doi:10.1016/j.matbio.2016.09.004.
122. Peng T, Frank DB, Kadzik RS, Morley MP, Rathi KS, Wang T, Zhou S, Cheng L, Lu MM, Morrisey EE. Hedgehog actively maintains adult lung quiescence and regulates repair and regeneration. Nature 526: 578-582, 2015. doi:10.1038/nature14984.
123. Perrin DG, McDonald TJ, Cutz E. Hyperplasia of bombesin-immunoreactive pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome. Pediatr Pathol 11: 431-447, 1991. doi:10.3109/15513819109064779.
124. Perrin S. Preclinical research: make mouse studies work. Nature 507: 423-425, 2014. doi:10.1038/507423a.
125. Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE. Tissue-engineered lungs for in vivo implantation. Science 329: 538-541, 2010. doi:10.1126/science.1189345.
126. Pifferi M, Montemurro F, Cangiotti AM, Ragazzo V, Di Cicco M, Vinci B, Vozzi G, Macchia P, Boner AL. Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia. Thorax 64: 1077-1081, 2009. doi:10.1136/thx.2008.110940.
127. Pizurki L, Morris MA, Chanson M, Solomon M, Pavirani A, Bouchardy I, Suter S. Cystic fibrosis transmembrane conductance regulator does not affect neutrophil migration across cystic fibrosis airway epithelial monolayers. Am J Pathol 156: 1407-1416, 2000. doi:10.1016/S0002-9440(10)65009-2.
128. Prakash YS, Tschumperlin DJ, Stenmark KR. Coming to terms with tissue engineering and regenerative medicine in the lung. Am J Physiol Lung Cell Mol Physiol 309: L625-L638, 2015. doi:10.1152/ajplung.00204.2015.
129. Rackley CR, Stripp BR. Building and maintaining the epithelium of the lung. J Clin Invest 122: 2724-2730, 2012. doi:10.1172/JCI60519.
130. Randell SH, Fulcher ML, O’Neal W, Olsen JC. Primary epithelial cell models for cystic fibrosis research. Methods Mol Biol 742: 285-310, 2011. doi:10.1007/978-1-61779-120-8_18.
131. Rawlins EL, Clark CP, Xue Y, Hogan BLM. The Id2_ distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 136: 3741-3745, 2009. doi:10.1242/dev.037317.
132. Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL, Hasegawa H, Wang F, Hogan BLM. The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4: 525-534, 2009. doi:10.1016/j.stem.2009.04.002.
133. Rawlins EL, Ostrowski LE, Randell SH, Hogan BLM. Lung development and repair: contribution of the ciliated lineage. Proc Natl Acad Sci USA 104: 410-417, 2007. doi:10.1073/pnas.0610770104.
134. Rawlins EL. The building blocks of mammalian lung development. Dev Dyn 240: 463-476, 2011. doi:10.1002/dvdy.22482.
135. Ren H, Birch NP, Suresh V. An optimised human cell culture model for alveolar epithelial transport. PLoS One 11: e0165225, 2016. doi:10.1371/journal.pone.0165225.
136. Ren X, Moser PT, Gilpin SE, Okamoto T, Wu T, Tapias LF, Mercier FE, Xiong L, Ghawi R, Scadden DT, Mathisen DJ, Ott HC. Engineering pulmonary vasculature in decellularized rat and human lungs. Nat Biotechnol 33: 1097-1102, 2015. doi:10.1038/nbt.3354.
137. Rock JR, Gao X, Xue Y, Randell SH, Kong Y-Y, Hogan BLM. Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell 8: 639-648, 2011. doi:10.1016/j.stem.2011.04.003.
138. Rock JR, Onaitis MW, Rawlins EL, Lu Y, Clark CP, Xue Y, Randell SH, Hogan BLM. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci USA 106: 12771-12775, 2009. doi:10.1073/pnas.0906850106.
139. Rockich BE, Hrycaj SM, Shih HP, Nagy MS, Ferguson MAH, Kopp JL, Sander M, Wellik DM, Spence JR. Sox9 plays multiple roles in the lung epithelium during branching morphogenesis. Proc Natl Acad Sci USA 110: E4456-E4464, 2013. doi:10.1073/pnas.1311847110.
140. Ruggeri BA, Camp F, Miknyoczki S. Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery. Biochem Pharmacol 87: 150-161, 2014. doi:10.1016/j.bcp.2013.06.020.
141. Rutland J, Cole PJ. Non-invasive sampling of nasal cilia for measurement of beat frequency and study of ultrastructure. Lancet 2: 564-565, 1980. doi:10.1016/S0140-6736(80)91995-9.
142. Sakao S, Tatsumi K, Voelkel NF. Endothelial cells and pulmonary arterial hypertension: apoptosis, proliferation, interaction and transdifferentiation. Respir Res 10: 95, 2009. doi:10.1186/1465-9921-10-95.
143. Schamberger AC, Staab-Weijnitz CA, Mise-Racek N, Eickelberg O. Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface. Sci Rep 5: 8163, 2015. doi:10.1038/srep08163.
144. Schwank G, Koo B-K, Sasselli V, Dekkers JF, Heo I, Demircan T, Sasaki N, Boymans S, Cuppen E, van der Ent CK, Nieuwenhuis EES, Beekman JM, Clevers H. Functional repair of CFTR by CRISPR/ Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13: 653-658, 2013. doi:10.1016/j.stem.2013.11.002.
145. Sekhon HS, Jia Y, Raab R, Kuryatov A, Pankow JF, Whitsett JA, Lindstrom J, Spindel ER. Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys. J Clin Invest 103: 637-647, 1999. doi:10.1172/JCI5232.
146. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S. Fgf10 is essential for limb and lung formation. Nat Genet 21: 138-141, 1999. doi:10.1038/5096.
147. Shah VS, Meyerholz DK, Tang XX, Reznikov L, Abou Alaiwa M, Ernst SE, Karp PH, Wohlford-Lenane CL, Heilmann KP, Leidinger MR, Allen PD, Zabner J, McCray PB Jr, Ostedgaard LS, Stoltz DA, Randak CO, Welsh MJ. Airway acidification initiates host defense abnormalities in cystic fibrosis mice. Science 351: 503-507, 2016. doi:10.1126/science.aad5589.
148. Snider GL. Collagen concentration and rates of synthesis in idiopathic pulmonary fibrosis. Am Rev Respir Dis 124: 341-342, 1981.
149. Snoeck H-W. Modeling human lung development and disease using pluripotent stem cells. Development 142: 13-16, 2015. doi:10.1242/dev.115469.
150. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470: 105-109, 2011. doi:10.1038/nature09691.
151. Stabler CT, Caires LC Jr, Mondrinos MJ, Marcinkiewicz C, Lazarovici P, Wolfson MR, Lelkes PI. Enhanced re-endothelialization of decellularized rat lungs. Tissue Eng Part C Methods 22: 439-450, 2016. doi:10.1089/ten.tec.2016.0012.
152. Tadokoro T, Gao X, Hong CC, Hotten D, Hogan BLM. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. Development 143: 764-773, 2016. doi:10.1242/dev.126656.
153. Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, Parton RG, Wolvetang EJ, Roost MS, Chuva de Sousa Lopes SM, Little MH. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526: 564-568, 2015. doi:10.1038/nature15695.
154. Tan Q, Choi KM, Sicard D, Tschumperlin DJ. Human airway organoid engineering as a step toward lung regeneration and disease modeling. Biomaterials 113: 118-132, 2017. doi:10.1016/j.biomaterials.2016.10.046.
155. Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M, Law BM, Vinarsky V, Cho JL, Breton S, Sahay A, Medoff BD, Rajagopal J. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature 503: 218-223, 2013. doi:10.1038/nature12777.
156. Thébaud B, Ladha F, Michelakis ED, Sawicka M, Thurston G, Eaton F, Hashimoto K, Harry G, Haromy A, Korbutt G, Archer SL. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation 112: 2477-2486, 2005. doi:10.1161/CIRCULATIONAHA.105.541524.
157. Tilley AE, Walters MS, Shaykhiev R, Crystal RG. Cilia dysfunction in lung disease. Annu Rev Physiol 77: 379-406, 2015. doi:10.1146/annurevphysiol-021014-071931.
158. Toskala E, Haataja J, Shirasaki H, Rautiainen M. Culture of cells harvested with nasal brushing: a method for evaluating ciliary function. Rhinology 43: 121-124, 2005.
159. Tovar JA. Congenital diaphragmatic hernia. Orphanet J Rare Dis 7: 1, 2012. doi:10.1186/1750-1172-7-1.
160. Trecartin A, Danopoulos S, Spurrier R, Knaneh-Monem H, Hiatt M, Driscoll B, Hochstim C, Al-Alam D, Grikscheit TC. Establishing proximal and distal regional identities in murine and human tissue-engineered lung and trachea. Tissue Eng Part C Methods 22: 1049-1057, 2016. doi:10.1089/ten.tec.2016.0261.
161. Truog WE, Xu D, Ekekezie II, Mabry S, Rezaiekhaligh M, Svojanovsky S, Soares MJ. Chronic hypoxia and rat lung development: analysis by morphometry and directed microarray. Pediatr Res 64: 56-62, 2008. doi:10.1203/PDR.0b013e31817289f2.
162. Van Goor F, Hadida S, Grootenhuis PDJ, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 106: 18825-18830, 2009. doi:10.1073/pnas.0904709106.
163. Varner VD, Gleghorn JP, Miller E, Radisky DC, Nelson CM. Mechanically patterning the embryonic airway epithelium. Proc Natl Acad Sci USA 112: 9230-9235, 2015. doi:10.1073/pnas.1504102112.
164. Varner VD, Nelson CM. Cellular and physical mechanisms of branching morphogenesis. Development 141: 2750-2759, 2014. doi:10.1242/dev.104794.
165. Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG, Treutlein B, Tan K, Tan V, Liu FC, Looney MR, Matthay MA, Rock JR, Chapman HA. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 517: 621-625, 2015. doi:10.1038/nature14112.
166. Vorotnikova E, McIntosh D, Dewilde A, Zhang J, Reing JE, Zhang L, Cordero K, Bedelbaeva K, Gourevitch D, Heber-Katz E, Badylak SF, Braunhut SJ. Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo. Matrix Biol 29: 690-700, 2010. doi:10.1016/j.matbio.2010.08.007.
167. Wagner DE, Bonenfant NR, Parsons CS, Sokocevic D, Brooks EM, Borg ZD, Lathrop MJ, Wallis JD, Daly AB, Lam YW, Deng B, DeSarno MJ, Ashikaga T, Loi R, Weiss DJ. Comparative decellularization and recellularization of normal versus emphysematous human lungs. Biomaterials 35: 3281-3297, 2014. doi:10.1016/j.biomaterials.2013.12.103.
168. Watson CL, Mahe MM, Múnera J, Howell JC, Sundaram N, Poling HM, Schweitzer JI, Vallance JE, Mayhew CN, Sun Y, Grabowski G, Finkbeiner SR, Spence JR, Shroyer NF, Wells JM, Helmrath MA. An in vivo model of human small intestine using pluripotent stem cells. Nat Med 20: 1310-1314, 2014. doi:10.1038/nm.3737.
169. Weiser N, Molenda N, Urbanova K, Bähler M, Pieper U, Oberleithner H, Schillers H. Paracellular permeability of bronchial epithelium is controlled by CFTR. Cell Physiol Biochem 28: 289-296, 2011. doi:10.1159/000331742.
170. Whitcutt MJ, Adler KB, Wu R. A biphasic chamber system for maintaining polarity of differentiation of cultured respiratory tract epithelial cells. In Vitro Cell Dev Biol 24: 420-428, 1988. doi:10.1007/BF02628493.
171. White ES. Lung extracellular matrix and fibroblast function. Ann Am Thorac Soc 12, Suppl 1: S30-S33, 2015. doi:10.1513/AnnalsATS.201406-240MG.
172. Whitsett JA, Kalinichenko VV. Notch and basal cells take center stage during airway epithelial regeneration. Cell Stem Cell 8: 597-598, 2011. doi:10.1016/j.stem.2011.05.008.
173. Wilkinson DC, Alva-Ornelas JA, Sucre JMS, Vijayaraj P, Durra A, Richardson W, Jonas SJ, Paul MK, Karumbayaram S, Dunn B, Gomperts BN. Development of a three-dimensional bioengineering technology to generate lung tissue for personalized disease modeling. Stem Cells Transl Med. 6: 622-633, 2017. doi:10.5966/sctm.2016-0192.
174. Willem M, Miosge N, Halfter W, Smyth N, Jannetti I, Burghart E, Timpl R, Mayer U. Specific ablation of the nidogen-binding site in the laminin gamma1 chain interferes with kidney and lung development. Development 129: 2711-2722, 2002.
175. Wolff RK. Effects of airborne pollutants on mucociliary clearance. Environ Health Perspect 66: 223-237, 1986. doi:10.1289/ehp.8666223.
176. Wong AP, Bear CE, Chin S, Pasceri P, Thompson TO, Huan L-J, Ratjen F, Ellis J, Rossant J. Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nat Biotechnol 30: 876-882, 2012. doi:10.1038/nbt.2328.
177. Workman MJ, Mahe MM, Trisno S, Poling HM, Watson CL, Sundaram N, Chang C-F, Schiesser J, Aubert P, Stanley EG, Elefanty AG, Miyaoka Y, Mandegar MA, Conklin BR, Neunlist M, Brugmann SA, Helmrath MA, Wells JM. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med 23: 49-59, 2017. doi:10.1038/nm.4233.
178. Yamaya M, Finkbeiner WE, Chun SY, Widdicombe JH. Differentiated structure and function of cultures from human tracheal epithelium. Am J Physiol Lung Cell Mol Physiol 262: L713-L724, 1992.