Idiopathic pulmonary fibrosis (IPF) is progressive fibrosing interstitial pneumonia of unknown cause, chronic and incurable interstitial lung disease, associated with high mortality rates and unresponsive to treatments currently available. The prevalence of IPF is estimated at approximately 20/100,000 in men and 13/100,000 in women, and the mean age at the time of diagnosis is 67 years and the median survival is 2 to 5 years. Therapies available to date, proved, therefore, only palliative measures with doubtful or unsatisfactory result. Many experimental models of pulmonary fibrosis are described. Bleomycin-induced pulmonary fibrosis is a widely used experimental model to identify and validate new therapeutic targets. We have induced pulmonary fibrosis by intratracheal bleomycin and late instillation of mesenchymal stem cells (MSC) from adipose tissue as a therapeutic proposal was used. MSC have the capacity to modulate inflammatory and immune response. Furthermore, the long-term effect of MSCs could also regulate and control to collagen deposition of the myofibroblasts, a final and pivo cell of pulmonary fibrosis. MSC from adipose tissue is an effective therapy to decrease collagen synthesis and expression in late stage of bleomycin-induced pulmonary fibrosis model, which may contribute to new therapeutic targets.
References
[1]
Meltzer, E.B. and Noble, P.W. (2008) Idiopathic Pulmonary Fibrosis. Orphanet Journal of Rare Diseases, 3, 8. http://dx.doi.org/10.1186/1750-1172-3-8
[2]
Gross, T.J. and Hunninghake, G.W. (2001) Idiopathic Pulmonary Fibrosis. The New England Journal of Medicine, 345, 517-525. http://dx.doi.org/10.1056/NEJMra003200
[3]
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. http://dx.doi.org/10.1016/j.biocel.2007.08.011
[4]
Klingsberg, R., Mutsaers, S. and Lasky, J. (2010) Current Clinical Trials for the Treatment of Idiopathic Pulmonary Fibrosis. Journal of Asian Pacific Society of Respirology, 15, 19-31. http://dx.doi.org/10.1111/j.1440-1843.2009.01672.x
[5]
Ley, B., Collard, H.R. and King Jr., T.E. (2011) Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine, 183, 431-440. http://dx.doi.org/10.1164/rccm.201006-0894CI
[6]
Pereira, C.A., Malheiros, T., Coletta, E.M., Ferreira, R.G., Rubin, A.S., Otta, J.S., et al. (2006) Survival in Idiopathic Pulmonary Fibrosis-Cytotoxic Agents Compared to Corticosteroids. Respiratory Medicine, 100, 340-347. http://dx.doi.org/10.1016/j.rmed.2005.05.008
[7]
Taskar, V.S. and Coultas, D.B. (2006) Is Idiopathic Pulmonary Fibrosis an Environmental Disease? Proceedings of the American Thoracic Society, 3, 293-298. http://dx.doi.org/10.1513/pats.200512-131TK
[8]
Selman, M., King, T.E. and Pardo, A. (2001) Idiopathic Pulmonary Fibrosis: Prevailing and Evolving Hypothesis about Its Pathogenesis and Implications for Therapy. Annals of Internal Medicine, 134, 136-151. http://dx.doi.org/10.7326/0003-4819-134-2-200101160-00015
[9]
Raghu, G., Collard, H.R., Egan, J.J., Martinez, F.J., Behr, J., Brown, K.K., et al. (2011) An Official ATS/ERJ/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management. American Journal of Respiratory and Critical Care Medicine, 183, 788-824. http://dx.doi.org/10.1164/rccm.2009-040GL
[10]
Noth, I. and Martinez, F.J. (2007) Recent Advances in Idiopathic Pulmonary Fibrosis. Chest, 132, 637. http://dx.doi.org/10.1378/chest.06-1927
[11]
Harari, S. and Caminati, A. (2010) IPF: New Insight on Pathogenesis and Treatment. Allergy, 65, 537-553. http://dx.doi.org/10.1111/j.1398-9995.2009.02305.x
[12]
Kim, D.S. (2006) Interstitial Lung Disease in Rheumatoid Arthritis: Recent Advances. Current Opinion in Pulmonary Medicine, 12, 346-353. http://dx.doi.org/10.1097/01.mcp.0000239552.55326.ee
[13]
Collard, H.R., King Jr., T.E., Bartelson, B.B., Vourlekis, J.S., Schwarz, M.I. and Brown, K.K. (2003) Changes in Clinical and Physiologic Variables Predict Survival in Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine, 168, 538-542. http://dx.doi.org/10.1164/rccm.200211-1311OC
[14]
Zhang, Y., Khan, D., Delling, J., et al. (2012) Mechanisms Underlying the Osteo- and Adipo-Differentiation of Human Mesenchymal Stem Cells. The Scientific World Journal, 2012, 1-14. http://dx.doi.org/10.1100/2012/793823
[15]
Schreml, S., Babilas, P., Fruth, S., et al. (2009) Harvesting Human Adipose Tissue-Derived Adult Stem Cells: Resection versus Liposuction. Cytotherapy, 11, 947-957. http://dx.doi.org/10.3109/14653240903204322
[16]
Krause, D.S., Theise, N.D., Collector, M.I., et al. (2001) Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell. Cell, 105, 369-377. http://dx.doi.org/10.1016/S0092-8674(01)00328-2
[17]
Loebinger, M.R. and Janes, S.M. (2007) Stem Cells for Lung Disease. Chest, 132, 279-285. http://dx.doi.org/10.1378/chest.06-2751
[18]
Gimble, J.M., Guilak, F. and Bunnell, B.A. (2010) Clinical and Preclinical Translation of Cell-Based Therapies Using Adipose Tissue-Derived Cells. Stem Cell Research & Therapy, 1, 19. http://dx.doi.org/10.1186/scrt19
[19]
King Jr., T.E., Pardo, A. and Selman, M. (2011) Idiopathic Pulmonary Fibrosis. The Lancet, 378, 1949-1961. http://dx.doi.org/10.1016/S0140-6736(11)60052-4
[20]
Liu, Z.J., Zhuge, Y. and Velazquez, O.C. (2009) Trafficking and Differentiation of Mesenchymal Stem Cells. Journal of Cellular Biochemistry, 106, 984-991. http://dx.doi.org/10.1002/jcb.22091
[21]
Körbling, M., Estrov, Z. and Champlin, R. (2003) Adult Stem Cells and Tissue Repair. Bone Marrow Transplant, 32, S23-S24. http://dx.doi.org/10.1038/sj.bmt.1703939
[22]
Kørbling, M. and Estrov, Z. (2003) Adult Stem Cells for Tissue Repair—A New Therapeutic Concept? The New England Journal of Medicine, 349, 570-582. http://dx.doi.org/10.1056/NEJMra022361
[23]
Punithavathi, D., Venkatesan, N. and Babu, M. (2000) Curcumin Inhibition of Bleomycin-Induced Pulmonary Fibrosis in Rats. British Journal of Pharmacology, 131, 169-172. http://dx.doi.org/10.1038/sj.bjp.0703578
[24]
Umezawa, H., Suhara, Y., Takita, T. and Maeda, K. (1996) New Antibiotics, Bleomycin A and B. Journal of Antibiotics, 19, 200-209.
[25]
Thrall, R.S., McCormick, J.R., Jack, R.M., McReynolds, R.A. and Ward, P.A. (1979) Bleomycin-Induced Pulmonary Fibrosis in the Rat: Inhibition by Indomethacin. The American Journal of Pathology, 95, 117-130.
[26]
Özyurt, H., Sögut, S., Yildirim, Z., Kart, L., Iraz, M., Amutçu, F., Temel, I., Özen, S., Uzun, A. and Akyol, Ö. (2004) Inhibitory Effect of Caffeic Acid Phenethyl Ester on Bleomycine-Induce Lung Fibrosis in Rats. Clinica Chimica Acta, 339, 65-75. http://dx.doi.org/10.1016/j.cccn.2003.09.015
[27]
Cutroneo, K.R. (2006) Evidence for TGF-Beta1 and Bleomycin Intracellular Signaling through Autocrine Regulation of Smad 3 Binding to the Proximal Promoter of the Smad 7 Gene. Journal of Cellular Biochemistry, 97, 933-939. http://dx.doi.org/10.1002/jcb.20594
[28]
Hubner, R.H., Gitter, W., El Mokhtari, N.E., Mathiak, M., Both, M., Bolte, H., et al. (2008) Standardized Quantification of Pulmonary Fibrosis in Histological Samples. BioTechniques, 44, 507-511, 514-517.
[29]
Martinez, J.A., Ramos, S.G., Meirelles, M.S., Verceze, A.V., Arantes, M.R. and Vannucchi, H. (2008) Effects of Quercetin on Bleomycin-Induced Lung Injury: A Preliminary Study. Jornal Brasileiro de Pneumologia, 34, 445-452. (In Portuguese)
[30]
King Jr., T.E., Behr, J., Brown, K.K., du Bois, R.M., Lancaster, L., de Andrade, J.A., et al. (2008) BUILD-1: A Randomized Placebo-Controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine, 177, 75-81. http://dx.doi.org/10.1164/rccm.200705-732OC
[31]
Kumar, V., Abbas, A.K. and Aster, J.C. (2015) Robbins & Cotran Pathologic Basis of Disease. 9th Edition, Elsevier, Philadelphia.
[32]
Singh, B., Shinagawa, K., Taube, C., Gelfand, E.W. and Pabst, R. (2005) Strain-Specific Differences in Perivascular Inflammation in Lungs in Two Murine Models of Allergic Airway Inflammation. Clinical and Experimental Immunology, 141, 223-229. http://dx.doi.org/10.1111/j.1365-2249.2005.02841.x
[33]
Raghu, G., Depaso, W.J., Cain, K., Hammar, S.P., Wetzel, C.E., Dreis, D.F., et al. (1991) Azathioprine Combined with Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis: A Prospective Double-Blind, Randomized, Placebo-Controlled Clinical Trial. The American Review of Respiratory Disease, 144, 291-296. http://dx.doi.org/10.1164/ajrccm/144.2.291
[34]
Raghu, G., Brown, K.K., Costabel, U., Cottin, V., du Bois, R.M., Lasky, J.A., et al. (2008) Treatment of Idiopathic Pulmonary Fibrosis with Etanercept: An Exploratory, Placebo-Controlled Trial. American Journal of Respiratory and Critical Care Medicine, 178, 948-955. http://dx.doi.org/10.1164/rccm.200709-1446OC
[35]
Singh, B., Shinagawa, K., Taube, C., Gelfand, E.W. and Pabst, R. (2005) Strain-Specific Differences in Perivascular Inflammation in Lungs in Two Murine Models of Allergic Airway Inflammation. Clinical and Experimental Immunology, 141, 223-229. http://dx.doi.org/10.1111/j.1365-2249.2005.02841.x
[36]
Antó, J.M. and Cullinan, P. (2001) Clusters, Classification and Epidemiology of Interstitial Lung Diseases: Concepts, Methods and Critical Reflections. European Respiratory Journal, 32, 101-106.