stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung
injury models; therefore, ESC, or their products, could be candidates for
regenerative therapy for incurable lung diseases, such as idiopathic pulmonary
fibrosis (IPF). In this study, we have investigated the paracrine effect of
differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC)
wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment
for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM)
which contain cell secretory factors were collected at different time points of
differentiation. CM were then tested onin vitro wound repair model with human type II
AEC line, A549 cells (AEC). Our study demonstrated that CM originated from
undifferentiated hESC significantly inhibited AEC wound repair when compared to
the control. Whereas, CM originated from Activin-directed hESC differentiated
cell population demonstrated a differential reparative effect on AEC wound
repair model. CM obtained from Day-11 of differentiation significantly enhanced
AEC wound repair in comparison to CM collected from pre- and post-Day-11 of
differentiation. Day-11 CM enhanced AEC wound repair through significant
stimulation of cell migration and cell proliferation. RT-PCR and
immunocytochemistry confirmed that Day-11 CM was originated form a mixed
population of endodermal/mesodermal differentiated hESC. This report suggests a
putative paracrine-mediated epithelial injury healing mechanism by hESC
secreted products, which is valuable in the development of novel stem
cell-based therapeutic strategies.
 Raghu, G., Collard, H.R., Egan, J.J., et al. (2011) ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. 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.
 Selman, M., King, T.E. and Pardo, A. (2001) American Thoracic Society, European Respiratory Society, American College of Chest Physicians. Idiopathic Pulmonary Fibrosis: Prevailing and Evolving Hypotheses about Its Pathogenesis and Implications for Therapy. Annals of Internal Medicine, 134, 136-151.
 Strieter, R.M. (2005) Pathogenesis and Natural History of Usual Interstitial Pneumonia: The Whole Story or the Last Chapter of a Long Novel. Chest, 128, 526S-532S. http://dx.doi.org/10.1378/chest.128.5_suppl_1.526S
 Mason, R.J. (2006) Biology of Alveolar Type II Cells. Respirology, Suppl. 11, S12-S15.
 Zahm, J.M., Chevillard, M. and Puchelle, E. (1991) Wound Repair of Human Surface Respiratory Epithelium. American Journal of Respiratory Cell and Molecular Biology, 5, 242-248. http://dx.doi.org/10.1165/ajrcmb/5.3.242
 Puchelle, E., Zahm, J.M., Tournier, J.M., et al. (2006) Airway Epithelial Repair, Regeneration, and Remodeling after Injury in Chronic Obstructive Pulmonary Disease. Proceedings of the American Thoracic Society, 3, 726-733.
 Crosby, L.M. and Waters, C.M. (2010) Epithelial Repair Mechanisms in the Lung. AJP—Lung Cellular and Molecular Physiology, 298, L715-L731.
 Corrin, B., Dewar, A., Rodriguez-Roisin, R., et al. (1985) Fine Structural Changes in Cryptogenic Fibrosing Alveolitis and Asbestosis. The Journal of Pathology, 147, 107-119. http://dx.doi.org/10.1002/path.1711470206
 Uhal, B.D., Joshi, I., Hughes, W.F., et al. (1998) Alveolar Epithelial Cell Death Adjacent to Underlying Myofibroblasts in Advanced Fibrotic Human Lung. American Journal of Physiology—Lung Cellular and Molecular Physiology, 275, L1192-L1199.
 Kuwano, K., Miyazaki, H., Hagimoto, N., et al. (1999) The Involvement of Fas-Fas Ligand Pathway in Fibrosing Lung Diseases. American Journal of Respiratory Cell and Molecular Biology, 20, 53-60.
 Barbas-Filho, J.V., Ferreira, M.A., Sesso, A., et al. (2001) Evidence of Type II Pneumocyte Apoptosis in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IFP)/Usual Interstitial Pneumonia (UIP). Journal of Clinical Pathology, 54, 132-138. http://dx.doi.org/10.1136/jcp.54.2.132
 Akram, K.M., Samad, S., Spiteri, M., et al. (2013) Mesenchymal Stem Cell Therapy and Lung Diseases. Advances in Biochemical Engineering/Biotechnology, 130, 105-29. http://dx.doi.org/10.1007/10_2012_140
 Akram, K.M., Lomas, N.J., Spiteri, M.A., et al. (2013) Club Cells Inhibit Alveolar Epithelial Wound Repair via TRAILDependent Apoptosis. European Respiratory Journal, 41, 683-694.
 Selman, M. and Pardo, A. (2002) Idiopathic Pulmonary Fibrosis: An Epithelial/Fibroblastic Cross-Talk Disorder. Respiratory Research, 3, 3. http://dx.doi.org/10.1186/rr175
 Odajima, N., Betsuyaku, T., Nasuhara, Y., et al. (2007) Loss of Caveolin-1 in Bronchiolization in Lung Fibrosis. Journal of Histochemistry & Cytochemistry, 55, 899-909. http://dx.doi.org/10.1369/jhc.7A7203.2007
 Chilosi, M., Poletti, V., Murer, B., Lestani, M., Cancellieri, A., Montagna, L., et al. (2002) Abnormal Re-Epithelialization and Lung Remodeling in Idiopathic Pulmonary Fibrosis: The Role of ?N-p63. Laboratory Investigation, 82, 1335-1345.