Idiopathic pulmonary fibrosis (IPF) is characterized by exuberant apoptosis and inadequate regeneration of lung parenchyma cells. Intratracheal alveolar type II epithelial cell instillation alleviates lung inflammation and fibrosis. Resident lung epithelial stem cells, as well as exogenous mesenchymal stem cells, are capable of differentiating into lung epithelial cells and repair the injured lung. It is thus supposed that, either engraftment of exogenous stem cells, or methods facilitating endogenous lung stem cell proliferation, are promising treatments for IPF, a devastating disease. Arrays of cellular and animal studies have shown the potential of stem cells in alleviating experimental lung fibrosis. Moreover, clinical trials have been launched to investigate the potentials of cell-based therapy in IPF patients. We intend to discuss the newest advances on stem cell therapy in pulmonary fibrosis, particularly the advantages, promises, and possible hurdles to pass from the successes in laboratory experiments to the eventual clinical applications.
Chen, X., Zhang, X., Li, X. and Wang, Z. (2013) Who and what should we rely on in early diagnosis of IPF? European Respiratory Journal, 41, 249-250. doi:10.1183/09031936.00142012
Nathan, S.D., Shlobin, O.A., Weir, N., Ahmad, S., Kaldjob, J.M., Battle, E., et al. (2011) Long-term course and prognosis of idiopathic pulmonary fibrosis in the new millennium. Chest, 140, 221-229. doi:10.1378/chest.10-2572
Raghu, G., Collard, H.R., Egan, J.J., Martinez, F.J., Behr, J., Brown, K.K., et al. (2011) An Official ATS/ERS/JRS/ ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. American Journal of Respiratory and Critical Care Medicine, 183, 788-824. doi:10.1164/rccm.2009-040GL
Behr, J. (2013) Evidence-based treatment strategies in idiopathic pulmonary fibrosis. European Respiratory Review, 22, 163-168. doi:10.1183/09059180.00001013
Spagnolo, P., Del Giovane, C., Luppi, F., Cerri, S., Balduzzi, S., Walters, E.H., et al. (2010) Non-steroid agents for idiopathic pulmonary fibrosis. Cochrane Database of Systematic Reviews, 9, Article ID: CD003134. doi:10.1002/14651858.CD003134.pub2
Nobel, P.W., Abera, C., Bradford, W.Z., Costabel, U., Glassberg, M.K., Kardatzke, D., et al. (2011) Pifernidone in patients with idiopathic pulmonary fibrosis (CAPAC-ITY): Two randomised trials. Lancet, 377, 1760-1769. doi:10.1016/S0140-6736(11)60405-4
Navaratnam, V., Fleming, K.M., West, J., Smith, C.J., Jenkins, R.G., Fogarty, A., et al. (2011) The rising incidence of idiopathic pulmonary fibrosis in the UK. Thorax, 66, 462-467. doi:10.1136/thx.2010.148031
Adamali, H.I. and Maher, T.M. (2012) Current and novel drug therapies for idiopathic pulmonary fibrosis. Drug Design, Development and Therapy, 6, 261-272. doi:10.2147/DDDT.S29928
Weiss, D.J., Berberich, M.A., Borok, Z., Stripp, B.R., Gail, D.B., Kolls, J.K., et al. (2006) Adult stem cells, lung biology, and lung disease. NHLBI/Cystic Fibrosis Foundation Workshop. Proceedings of the American Thoracic Society, 3, 193-207. doi:10.1513/pats.200601-013MS
Weiss, D.J., Kolls, J.K., Ortiz, L.A., Panoskaltsis-Mortari, A. and Prockop, D.J. (2008) Stem cells and cell therapies in lung biology and lung diseases. Proceedings of the American Thoracic Society, 5, 637-667. doi:10.1513/pats.200804-037DW
Weiss, D.J., Bertoncello, I., Borok, Z., Kim, C., Panoskaltsis-Mortari, A., Reynolds, S., et al. (2011) Stem cells and cell therapies in lung biology and lung diseases. Proceedings of the American Thoracic Society, 8, 223-272. doi:10.1513/pats.201012-071DW
Matthay, M.A., Thompson, B.T., Read, E.J., McKenna, D.H. Jr., Liu, K.D., Calfee, C.S., et al. (2010) Therapeutic potential of mesenchymal stem cells for severe acute lung injury. Chest, 138, 965-972. doi:10.1378/chest.10-0518
Lee, J.W., Fang, X., Gupta, N., Serikov, V. and Matthay, M.A. (2009) Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proceedings of the National Academy of Sciences of USA, 106, 16357-16362. doi:10.1073/pnas.0907996106
Ishizawa, K., Kubo, H., Yamada, M. Kobayashi, S., Numasaki, M., Ueda, S., et al. (2004) Bone marrow derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Letters, 556, 249-252. doi:10.1016/S0014-5793(03)01399-1
Zhen, G., Liu, H., Gu, N., Zhang, H., Xu, Y. and Zhang, Z. (2008) Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Frontiers in Bioscience, 13, 3415-3422. doi:10.2741/2936
Schweitzer, K.S., Johnstone, B.H., Garrison, J., Rush, N.I., Cooper, S., Traktuev, D.O., et al. (2011) Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. American Journal of Respiratory and Critical Care Medicine, 183, 215-225. doi:10.1164/rccm.201001-0126OC
Sueblinvong, V., Loi, R., Eisenhauer, P.L., Bernstein, I.M., Suratt, B.T., Spees, J.L., et al. (2008) Derivation of lung epithelium from human cord blood-derived mesenchymal stem cells. American Journal of Respiratory and Critical Care Medicine, 177, 701-711. doi:10.1164/rccm.200706-859OC
Bonfield, T.L., Koloze, M., Lennon, D.P., Zuchowski, B., Yang, S.E. and Caplan, A.I. (2010) Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. American Journal of Physiology-Lung Cellular and Molecular Physiology, 299, L760-L770. doi:10.1152/ajplung.00182.2009
Ortiz, L.Z., Gambelli, F., McBride, C., Gaupp, D., Baddoo, M., Kaminski, N., et al. (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proceedings of the National Academy of Sciences of USA, 100, 8407-8411. doi:10.1073/pnas.1432929100
Tzouvelekis, A., Koliakos, G., Ntolios, P., Baira, I., Bouros, E., Oikonomou, A., et al. (2011) Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal. Journal of Translational Medicine, 9, 182. doi:10.1186/1479-5876-9-182
Tzouvelekis, A., Paspaliaris, V., Koliakos, G., Ntolios, P., Oikonomou, A., Froudarakis, M., et al. (2011) A prospective, non randomized, clinical trial to study the safety and efficacy of the endobronchial autologous infusion of adipose-derived mesenchymal stem cells (ADMSCs) in patients with idiopathic pulmonary fibrosis (IPF). European Respiratory Journal, 176, 3s.
Gharaee-Kermani, M., Gyetko, M.R., Hu, B. and Phan, S.H. (2007) New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: A potential role for stem cells in the lung parenchyma and implications for therapy. Pharmaceutical Research, 24, 819-841. doi:10.1007/s11095-006-9216-x
Tzouvelekis, A., Antoniadis, A. and Bouros, D. (2011) Stem cell therapy in pulmonary fibrosis. Current Opinion in Pulmonary Medicine, 17, 368-373. doi:10.1097/MCP.0b013e328348744f
Toonkel, R.L., Hare, J.M., Matthay, M.A. and Glassberg, M.K. Mesenchymal stem cells and idiopathic pulmonary fibrosis: potential for clinical testing. (2013) American Journal of Respiratory and Critical Care Medicine, 188, 133-140. doi:10.1164/rccm.201207-1204PP
Giangreco, A., Reynolds, S.D. and Stripp, B.R. (2002) Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. American Journal of Pathology, 161, 173-182. doi:10.1016/S0002-9440(10)64169-7
Hong, K.U., Reynolds, S.D., Watkins, S., Fuchs, E. and Stripp, B.R. (2004) Basal cells are a multipotent progenytor capable of renewing the bronchial epithelium. American Journal of Pathology, 164, 577-588. doi:10.1016/S0002-9440(10)63147-1
Kim, C.F., Jackson, E.L., Woolfenden, A.E., et al. (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell, 121, 823-835. doi:10.1016/j.cell.2005.03.032
Kajstura, J., Rota, M., Hall, S.R., Hosoda, T., D’Amario, D., Sanada, F., et al. (2011) Evidence for human lung stem cells. The New England Journal of Medicine, 364, 1795-1806. doi:10.1056/NEJMoa1101324
Olsson, F., Denham, M., Cole, T.J., Hooper, S.B. and Mollard, R. (2007) Deriving respiratory cell types from stem cells. Current Stem Cell Research & Therapy, 2, 197-208. doi:10.2174/157488807781696203
Gomperts, B.N. and Strieter, R.M. (2007) Stem cells and chronic lung disease. Annual Review of Medicine, 58, 285-298. doi:10.1146/annurev.med.58.081905.134954
Krause, D.S., Theise, N.D., Collector, M.I., Henegariu, O., Hwang, S., Gardner, R., et al. (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 105, 369-377. doi:10.1016/S0092-8674(01)00328-2
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315-317. doi:10.1080/14653240600855905
Le Blanc, K., Tammik, C., Rosendahl, K., Zetterberg, E. and Ringdén, O. (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Experimental Hematology, 31, 890-896. doi:10.1016/S0301-472X(03)00110-3
Brody, A.R., Salazar, K.D. and Lankford, S.M. (2010) Mesenchymal stem cells modulating lung injury. Proceedings of the American Thoracic Society, 7, 130-133. doi:10.1513/pats.200908-091RM
Garcia-Gomez, I., Elvira, G., Zapata, G., Lamana, M.L., Ramirez, M., Castro, J.G., et al. (2010) Mesenchymal stem cells: Biological properties and clinical applications. Expert Opinion on Biological Therapy, 10, 1453-1468. doi:10.1517/14712598.2010.519333
Sueblinvong, V., Loi, R., Eisenhauer, P.L., Bernstein, I.M., Suratt, B.T., Spees, J.L., et al. (2008) Derivation of lung epithelium from human cord blood-derived mesenchymal stem cells. American Journal of Respiratory and Critical Care Medicine, 177, 701-711. doi:10.1164/rccm.200706-859OC
Newman, R.E., Yoo, D., LeRoux, M.A. and Danilkovitch-Miagkova, A. (2009) Treatment of inflammatory diseases with mesenchymal stem cells. Inflammation & Allergy—Drug Targets, 8, 110-123. doi:10.2174/187152809788462635
Togel, F., Hu, Z., Weiss, K., Isaac, J., Lange, C. and Westenfelder, C. (2005) Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. American Journal of Physiology—Renal Physiology, 289, F31-F42. doi:10.1152/ajprenal.00007.2005
Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., et al. (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nature Medicine, 12, 459-465. doi:10.1038/nm1391
American Thoracic Society, European Respiratory Society (2002) American thoracic society/European respiretory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. American Journal of Respiratory and Critical Care Medicine, 165, 277-304. doi:10.1164/ajrccm.165.2.ats01
Selman, M., King Jr., T.E. and Pardo, A. (2001) Idiopathic pulmonary fibrosis: Prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Annals of Internal Medicine, 134, 136-151. doi:10.7326/0003-4819-134-2-200101160-00015
Kalluri, R. and Neilson, E.G. (2003) Epithelial-mesenchymal transition and its implications for fibrosis. Journal of Clinical Investigation, 112, 1776-1784. doi:10.1172/JCI200320530
Selman, M., Pardo, A. and Kaminshi, N. (2008) Idiopathic pulmonary fibrosis: Aberrant recapitulation of developmental programs? PLoS Medicine, 5, e62. doi:10.1371/journal.pmed.0050062
Wuyts, W.A., Agostini, C., Antoniou, K.M., Bouros, D., Chambers, R.C., Cottin, V., et al. (2013) The pathogenesis of pulmonary fibrosis: A moving target. European Respiratory Journal, 41, 1207-1218. doi:10.1183/09031936.00073012
Moore, B.B. and Hogaboam, C.M. (2008) Murine models of pulmonary fibrosis. American Journal of Physiology— Lung Cellular and Molecular Physiology, 294, L152L160. doi:10.1152/ajplung.00313.2007
Uhal, B.D. (2008) The role of apoptosis in pulmonary fibrosis. European Respiratory Review, 17, 138-144. doi:10.1183/09059180.00010906
Sisson, T.H., Mendez, M., Choi, K., Subbotina, N., Courey, A., Cunningham, A., et al. (2010) Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 181, 254-263. doi:10.1164/rccm.200810-1615OC
Chilosi, M., Doglioni, C., Murer, B. and Poletti, V. (2010) Epithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary fibrosis. Sarcoidosis, Vasculitis and Diffuse Lung Diseases, 27, 7-18.
Jun, D., Garat, C., West, J., Thorn, N., Chow, K., Cleaver, T., et al. (2011) The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation. Stem Cell, 29, 725-735. doi:10.1002/stem.604
Lee, S.H., Jang, A.S., Kim, Y.E., Cha, J.Y., Kim, T.H., Jung, S., et al. (2010) Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/ fibrosis. Respiratory Research, 8, 16. doi:10.1186/1465-9921-11-16
Zhao, F., Zhang, Y.F., Liu, Y.G., Zhou, J.J., Li, Z.K., Wu, C.G., et al. (2008) Therapeutic effects of bone marrowderived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplantation Proceedings, 40, 1700-1705. doi:10.1016/j.transproceed.2008.01.080
Wang, S., Qu, X. and Zhao, C. (2012) Clinical applications of mesenchymal stem cells. Journal of Hematology & Oncology, 5, 19. doi:10.1186/1756-8722-5-19
Kotton, D.N., Ma, B.Y., Cardoso, W.V., Sanderson, E.A., Summer, R.S., Williams, M.C., et al. (2001) Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development, 128, 5181-5188.
Spees, J.L., Pociask, D.A., Sullivan, D.E., Whitney, M.J., Lasky, J.A., Prockop, D.J., et al. (2007) Engraftment of bone marrow progenitor cells in a rat model of asbestosinduced pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 176, 385-394. doi: 10.1164/rccm.200607-1004OC
Kumamoto, M., Nishiwaki, T., Matsuo, N., Kimura, H. and Matsushima, K. (2009) Minimally cultured bone marrow mesenchymal stem cells ameliorate fibrotic lung injury. European Respiratory Journal, 34, 740-748. doi:10.1183/09031936.00128508
Moodley, Y., Ilancheran, S., Samuel, C., Vaghjiani, V., Atienza, D., Williams, E.D., et al. (2010) Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair. American Journal of Respiratory and Critical Care Medicine, 182, 643-651. doi:10.1164/rccm.201001-0014OC
Cargnoni, A., Gibelli, L., Tosini, A., Signoroni, P.B., Nassuato, C., Arienti, D., et al. (2009) Transplantation of allogeneic and xenogeneic placenta-derived cells reduces bleomycin-induced lung fibrosis. Cell Transplantation, 18, 405-422. doi:10.3727/096368909788809857
Rojas, M., Xu, J., Woods, C.R., Mora, A.L., Spears, W., Roman, J., et al. (2005) Bone-marrow-derived mesenchymal stem cells in repair of the injured lung. American Journal of Respiratory Cell and Molecular Biology, 33, 145-152. doi:10.1165/rcmb.2004-0330OC
Moodley, Y., Atienza, D., Manuelpillai, U., Samuel, C.S., Tchongue, J., Ilancheran, S., et al. (2009) Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. American Journal of Pathology, 175, 303-313. doi:10.2353/ajpath.2009.080629
Banerjee, E.R., Laflamme, M.A., Papayannopoulou, T., Kahn, M., Murry, C.E. and Henderson Jr., W.R. (2012) Human embryonic stem cells differentiated to lung lineage-specific cells ameliorate pulmonary fibrosis in a xenograft transplant mouse model. PLoS ONE, 7, e33165. doi:10.1371/journal.pone.0033165
Spitalieri, P., Quitadamo, M.C., Orlandi, A., Guerra, L., Giardina, E., Casavola, V., et al. (2012) Rescue of murine silica-induced lung injury and fibrosis by human embryonic stem cells. European Respiratory Journal, 39, 446-457. doi:10.1183/09031936.00005511
Hare, J.M., Traverse, J.H., Henry, T.D., Dib, N., Strumpf, R.K., Schulman, S.P., et al. (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Journal of the American College of Cardiology, 54, 2277-2286. doi:10.1016/j.jacc.2009.06.055
Hare, J.M., Fishman, J.E., Gerstenblith, G., DiFede Velazquez, D.L., Zambrano, J.P., Suncion, V.Y., et al. (2012) Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transcendocardial injection in patients with ischemic cardiomyopathy: The POSEIDON randomized trial. JAMA, 308, 2369-2379. doi:10.1001/jama.2012.25321
Weiss, D.J., Casaburi, R., Flannery, R., Leroux-Williams, M. and Tashkin, D.P. (2013) A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest, 143, 1590-1598. doi:10.1378/chest.12-2094
Chaudhary, N.I., Schnapp, A. and Park, J.E. (2006) Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model. American Journal of Respiratory and Critical Care Medicine, 173, 769-776. doi:10.1164/rccm.200505-717OC
Moeller, A., Ask, K., Warburton, D., Gauldie, J. and Kolb, M. (2008) The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis? The International Journal of Biochemistry & Cell Biology, 40, 362-382. doi:10.1016/j.biocel.2007.08.011
Borzone, G., Moreno, R., Urrea, R., Meneses, M., Oyarzun, M. and Lisboa, C. (2000) Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 163, 1648-1653. doi:10.1164/ajrccm.163.7.2006132
Chua, F., Gauldie, J. and Laurent, G.J. (2005) Pulmonary fibrosis: Searching for model answers. American Journal of Respiratory Cell and Molecular Biology, 33, 9-13. doi:10.1165/rcmb.2005-0062TR
Degryse, A.L., Tanjore, H., Xu, X.C., Polosukhin, V.V., Jones, B.R., McMahon, F.B., et al. (2010) Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis. American Journal of Physiology—Lung Cellular and Molecular Physiology, 299, L442-L452. doi:10.1152/ajplung.00026.2010
International Society for Stem Cell Research, Guidelines for the clinical translation of stem cells. http://www.isscr.org/home/publications/ClinTransGuide
Loebinger, M.R. and Janes, S.M. (2007) Stem cells for lung disease. Chest, 132, 279-285. doi:10.1378/chest.06-2751
Price, A.P., England, K.A., Matson, A.M., Blazar, B.R. and Panoskaltsis-Mortari, A. (2010) Development of a decellularized lung bioreactor system for bioengineering the lung: The matrix reloaded. Tissue Engineering Part A, 16, 2581-2591. doi:10.1089/ten.tea.2009.0659
Ling, L., Nurcombe, V. and Cool, S.M. (2009) Wnt signaling controls the fate of mesenchymal stem cells. Gene, 433, 1-7. doi:10.1016/j.gene.2008.12.008
Walker, N., Badri, L., Wettlaufer, S., Flint, A., Sajjan, U., Krebsbach, P.H., et al. (2011) Resident tissue-specific mesenchymal progenitor cells contribute to fibrogenesis in human lung allografts. American Journal of Pathology, 178, 2461-2469. doi:10.1016/j.ajpath.2011.01.058
Foronjy, R.F. and Majka, S.M. (2012) The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: Understanding microenvironmental cues. Cells, 1, 874. doi:10.3390/cells1040874
Warburton, D., Perin, L., DeFilippo, R., Bellusci, S., Shi, W. and Driscoll, B. (2008) Stem/progenitor cells in lung development, injury repair, and regeneration. Proceedings of the American Thoracic Society, 5, 703-706. doi:/10.1513/pats.200801-012AW
Grove, J.E., Lutzko, C., Priller, J., Henegariu, O., Theise, N.D., Kohn, D.B. et al. (2002) Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. American Journal of Respiratory Cell and Molecular Biology, 27, 645-651. doi:10.1165/rcmb.2002-0056RC
Loi, R., Beckett, T., Goncz, K.K., Suratt, B.T. and Weiss, D.J. (2006) Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells. American Journal of Respiratory and Critical Care Medicine, 173, 171-179. doi:10.1164/rccm.200502-309OC
Aguilar, S., Scotton, C.J., McNulty, K., Nye, E., Stamp, G., Laurent, G., et al. (2009) Bone marrow stem cells expressing keratinocyte growth factor via an inducible lentivirus protects against bleomycin-induced pulmonary fibrosis. PLoS ONE, 4, e8013. doi:10.1371/journal.pone.0008013
Konigshoff, M., Kramer, M., Balsara, N., Wilhelm, J., Amarie, O.V., Jahn, A., et al. (2010) WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. The Journal of Clinical Investigation, 119, 772-787. doi:10.1172/JCI33950
Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, M.A., Rees, L.E., Cogan, T.A., et al. (2008) Clinical transplantation of a tissue-engineered airway. Lancet, 372, 2023-2030. doi:10.1016/S0140-6736(08)61598-6
Andrade, C.F., Wong, A.P., Waddell, T.K., Keshavjee, S. and Liu, M. (2007) Cell-based tissue engineering for lung regeneration. American Journal of Physiology—Lung Cellular and Molecular Physiology, 292, 510-518. doi:10.1152/ajplung.00175.2006
Yu, W., Fang, X., Ewald, A., Wong, K., Hunt, C.A., Werb, Z., et al. (2007) Formation of cysts by alveolar type II cells in three-dimensional culture reveals a novel mechanism for epithelial morphogenesis. Molecular Biology of the Cell, 18, 1693-1700. doi:10.1091/mbc.E06-11-1052
Nichols, J.E. and Cortiella, J. (2008) Engineering of a complex organ: Progress toward development of a tissueengineered lung. Proceedings of the American Thoracic Society, 5, 723-730. doi:10.1513/pats.200802-022AW