Effects of transplanted mesenchymal stem cells on repair of the lung tissue of rats with experimental pulmonary fibrosis

  • Y. V. Surtaieva National University of Life and Environmental Sciences of Ukraine
  • A. Y. Mazurkevich National University of Life and Environmental Sciences of Ukraine
  • R. R. Bokotko National University of Life and Environmental Sciences of Ukraine
Keywords: bronchoalveolar lavage; pulmonary fibrosis; alogeneic mesenchymal stem cells; macrophages; regeneration; cellular therapy


Pulmonary fibrosis is one of the commonest forms of interstitial lung diseases with poorly studied methods of its treatment in both human and veterinary medicines. Therefore, this paper focused on seeking alternative methods of its diagnostics and treatment. The article provides the results of the study of bronchoalveolar lavage fluid of rats with experimental lung fibrosis and influence of transplanted allogeneic mesenchymal stem cells of the bone marrow on stimulation of regenerative processes in damaged lung tissues. The studies were conducted on female Wistar rats with pulmonary fibrosis modeled using single transthoracic injection of solution of bleomycin hydrochloride. For the purpose of treatment, we used allogeneic mesenchymal stem cells introduced by various methods and the traditional treatment. We determined that best normalization of the parameters of the studied brochoalveolar lavage occurred in animals that received mesenchymal stem cells. The most active repair processes were in the experimental group that received the mesenchymal stem cells directly to the lung tissue. The animals that received intravenous injection of mesenchymal stemm cells were observed to have lower clinical parameters of the brochoalveolar lavage, but still better than such in the group treated traditionally. The lowest parameters were in animals that received the traditional treatment; they were greater than the phisological parameters, but significantly exceeded them in animals of the control group, indicating presence of inflammatory process in the lung tissue. The conducted cytological assays of the samples of the brochoalveolar lavage revealed that experimental animals with experimental pulmonary fibrosis had development of macrophage and lymphocytic reactions under the influence of transplanted mesenchymal stemm cells. We observed no atypical cells in all the experimental groups. This allows us to draw a conclusion that using stem cells by various methods of transplantation does not stimulate the onset of negative reactons (formation of atypical cells, metastatic processes, etc). Thus, the results of the study of the influence of transplanted mesenchymal stem cells demonstrate that in the conditions of experimental pulmonary fibrosis, the activity of regenerative processes in pathologically altered lung tissue may be an effective method of treatment of animals with this kind of pathology.


Akram, K. M., Samad, S., Spiteri, M. A., & Forsyth, N. R. (2013). Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms. Respiratory Research, 14(1), 9.
Alcayaga-Miranda, F., Cuenca, J., & Khoury, M. (2017). Antimicrobial activity of mesenchymal stem cells: Current status and new perspectives of antimicrobial peptide-based therapies. Frontiers in Immunology, 8, 339.
Alvarez-Palomo, B., Sanchez-Lopez, L. I., Moodley, Y., Edel, M. J., Edel, M. J., Edel, M. J., Serrano-Mollar, A., & Serrano-Mollar, A. (2020). Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis. Stem Cell Research and Therapy, 11(1), 213–225.
Banerjee, E. R., Laflamme, M. A., Papayannopoulou, T., Kahn, M., Murry, C. E., & Henderson, 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(3), е33165.
Bedoret, D., Wallemacq, H., Marichal, T., Desmet, C., Calvo, F. Q., Henry, E., Closset, R., Dewals, B., Thielen, C., Gustin, P., De Leval, L., Van Rooijen, N., Le Moine, A., Vanderplasschen, A., Cataldo, D., Drion, P., Moser, M., Lekeux, P., & Bureau, F. (2009). Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. Journal of Clinical Investigation, 119(12), 3723–3738.
Bernardo, M. E., & Fibbe, W. E. (2013). Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell, 13(4), 392–402.
Boiko, D. N., Boiko, N. H., & Boiko, O. S. (2013). Sposib modeliuvannia fibrozu lehen u shchuriv [A method of modeling lung fibrosis in rats]. Patent 79901: A61D 99/00, G09B 23/00, Ukraina (in Ukrainian).
Bonfield, T. L., & Caplan, A. I. (2010). Adult mesenchymal stem cells: An innovative therapeutic for lung diseases. Discovery Medicine, 47(9), 337–345.
Bruder, S. P., Kurth, A. A., Shea, M., Hayes, W. C., Jaiswal, N., & Kadiyala, S. (1998). Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. Journal of Orthopaedic Research, 16(2), 155–162.
Cahill, E. F., Kennelly, H., Carty, F., Mahon, B. P., & English, K. (2016). Hepatocyte growth factor is required for mesenchymal stromal cell protection against bleomycin-induced pulmonary fibrosis. Stem Cells Translational Medicine, 5(10), 1307–1318.
Chambers, D. C., Enever, D., Ilic, N., Sparks, L., Whitelaw, K., Ayres, J., Yerkovich, S., Khalil, D., Atkinson, K., & Hopkins, P. M. A. (2014). A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology, 19(7), 1013–1018.
Chang, Y. S., Choi, S. J., Sung, D. K., Kim, S. Y., Oh, W., Yang, Y. S., & Park, W. S. (2011). Intratracheal transplantation of human umbilical cordblood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats. Cell Transplantation, 20, 1843–1854.
Chang, Y. S., Oh, W., Choi, S. J., Sung, D. K., Kim, S. Y., Choi, E. Y., Kang, S., Jin, H., Yang, Y., & Park, W. S. (2009). Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats. Cell Transplantation, 18(8), 869–886.
Chen, S., Cui, G., Peng, C., Lavin, M. F., Sun, X., Zhang, E., Yang, Y., Guan, Y., Du, Z., & Shao, H. (2018). Transplantation of adipose-derived mesenchymal stem cells attenuates pulmonary fibrosis of silicosis via anti-inflammatory and anti-apoptosis effects in rats. Stem Cell Research and Therapy, 9(1), 110–122.
Chimenti, L., Luque, T., Bonsignore, M. R., Ramírez, J., Navajas, D., & Farre, R. (2012). Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury. European Respiratory Journal, 40(4), 939–948.
Cruz, F. F., & Rocco, P. R. M. (2017). Stem-cell extracellular vesicles and lung repair. Stem Cell Investigation. AME Publishing Company, 9(4), 78–79.
Davidson, K. R., Ha, D. M., Schwarz, M. I., & Chan, E. D. (2020). Bronchoalveolar lavage as a diagnostic procedure: A review of known cellular and molecular findings in various lung diseases. Journal of Thoracic Disease, 12(9), 4991–5019.
de Witte, S. F. H., Luk, F., Sierra Parraga, J. M., Gargesha, M., Merino, A., Korevaar, S. S., Shankar, A., O’Flynn, L., Elliman, S., Roy, D., Betjes, M., Newsome, P., Baan, C., & Hoogduijn, M. J. (2018). Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells. Stem Cells, 36(4), 602–615.
Deans, R. J., & Moseley, A. B. (2000). Mesenchymal stem cells: Biology and potential clinical uses. Experimental Hematology, 28(8), 875–884.
Galleu, A., Riffo-Vasquez, Y., Trento, C., Lomas, C., Dolcetti, L., Cheung, T. S., Von Bonin, M., Barbieri, L., Halai, K., Ward, S., Weng, L., Chakraverty, R., Lombardi, G., Watt, F., Orchard, K., Marks, D., Apperley, J., Bornhauser, M., Walczak, H., Bennett, C., & Dazzi, F. (2017). Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Science Translational Medicine, 9, 416.
Ghaedi, M., Mendez, J. J., Bove, P. F., Sivarapatna, A., Raredon, M. S. B., & Niklason, L. E. (2014). Alveolar epithelial differentiation of human induced pluripotent stem cells in a rotating bioreactor. Biomaterials, 35(2), 699–710.
Guilliams, M., De Kleer, I., Henri, S., Post, S., Vanhoutte, L., De Prijck, S., Deswarte, K., Malissen, B., Hammad, H., & Lambrecht, B. N. (2013). Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. Journal of Experimental Medicine, 210(10), 1977–1992.
Harrell, C. R., Sadikot, R., Pascual, J., Fellabaum, C., Jankovic, M. G., Jovicic, N., Djonov, V., Arsenijevic, N., & Volarevic, V. (2019). Mesenchymal stem cell-based therapy of inflammatory lung diseases: Current understanding and future perspectives. Stem Cells International, 2, 4236973.
Henderson, R. F. (2005). Use of bronchoalveolar lavage to detect respiratory tract toxicity of inhaled material. Experimental and Toxicologic Pathology, 57(S1), 155–159.
Huang, S. X. L., Islam, M. N., O’Neill, J., Hu, Z., Yang, Y. G., Chen, Y. W., Mumau, M., Green, M., Vunjak-Novakovic, G., Bhattacharya, J., & Snoeck, H. W. (2014). Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nature Biotechnology, 32(1), 84–91.
Huang, X., Sun, K., Zhao, Y. D., Vogel, S. M., Song, Y., Mahmud, N., & Zhao, Y. Y. (2014). Human CD34+ progenitor cells freshly isolated from umbilical cord blood attenuate inflammatory lung injury following LPS challenge. PLoS One, 9(2), e88814.
Inamdar, A. C., & Inamdar, A. A. (2013). Mesenchymal stem cell therapy in lung disorders: Pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell. Experimental Lung Research, 39(8), 315–327.
Jacob, A., Morley, M., Hawkins, F., Guttentag, S. H., Beers, M. F., & Kotton, D. N. (2017). Differentitation of human pluripotent stem cells into functional lung alveolar epithelial cells. Cell Stem Cell, 21(4), 472–488.
Jeong, J. O., Han, J. W., Kim, J. M., Cho, H. J., Park, C., Lee, N., Kim, D., & Yoon, Y. S. (2011). Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circulation Research, 108(11), 1340–1347.
Jun, D., Garat, C., West, J., Thorn, N., Chow, K., Cleaver, T., Sullivan, T., Torchia, E. C., Childs, C., Shade, T., Tadjali, M., Abigail, L., Nozik-Grayck, E., Malkoski, S., Sorrentino, B., Meyrick, B., Klemm, D., Rojas, M., David, H., Wagner Jr., & Majka, S. M. (2011). The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation. Stem Cells, 29(4), 725–735.
Katsha, A. M., Ohkouchi, S., Xin, H., Kanehira, M., Sun, R., Nukiwa, T., & Saijo, Y. (2011). Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Molecular Therapy, 19(1), 196–203.
Kim, H. J., Perlman, D., & Tomic, R. (2015). Natural history of idiopathic pulmonary fibrosis. Respiratory Medicine, 109(6), 661–670.
Kinder, B. W., Brown, K. K., Schwarz, M. I., Ix, J. H., Kervitsky, A., & King, T. E. (2008). Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest, 133(1), 226–232.
Kodavanti, U. P. (2014). Respiratory toxicity biomarkers. In: Biomarkers in toxicology. Academic Press. Pp. 217–239.
Krause, D. S., Theise, N. D., Collector, M. I., Henegariu, O., Hwang, S., Gardner, R., Neutzel, S., & Sharkis, S. J. (2001). Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 105(3), 369–377.
Lan, Y. W., Choo, K. B., Chen, C. M., Hung, T. H., Chen, Y. B., Hsieh, C. H., Kuo, H., & Chong, K. Y. (2015). Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis. Stem Cell Research and Therapy, 6(1), 97.
Laskin, D. L., Malaviya, R., & Laskin, J. D. (2019). Role of macrophages in acute lung injury and chronic fibrosis induced by pulmonary toxicants. Toxicological Sciences, 168(2), 287–301.
Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M., Remberger, M., Dini, G., Egeler, R., Bacigalupo, A., Fibbe, W., & Ringdén, O. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study. The Lancet, 371(9624), 1579–1586.
Lederer, D. J., & Martinez, F. J. (2009). Idiopathic pulmonary fibrosis. New England Journal of Medicine, 378(19), 1811–1823.
Lee, S. H., Jang, A. S., Kim, Y. E., Cha, J. Y., Kim, T. H., Jung, S., Park, S., Lee, Y., Won, J., Kim, Y., & Park, C. S. (2010). Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis. Respiratory Research, 11(1), 16.
Leibacher, J., & Henschler, R. (2016). Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells Mesenchymal Stem/Stromal Cells – An update. Stem Cell Research and Therapy, 7(1), 7.
Li, M., Li, Y. H., Hou, Y., Sun, X. F., Sun, Q., & Wang, W. H. (2004). Isolation and culture of pluripotent cells from in vitro produced porcine embryos. Zygote, 12(1), 43–48.
Lu, Q., & El-Hashash, A. H. K. (2019). Cell-based therapy for idiopathic pulmonary fibrosis. Stem Cell Investigation, 16(6), 22.
Luk, F., De Witte, S. F. H., Korevaar, S. S., Roemeling-Van Rhijn, M., Franquesa, M., Strini, T., Van Den Engel, S., Gargesha, M., Roy, D., Dor, F., Horwitz, E., De Bruin, R., Betjes, M., Baan, C., & Hoogduijn, M. J. (2016). Inactivated mesenchymal stem cells maintain immunomodulatory capacity. Stem Cells and Development, 25(18), 1342–1354.
Martinez, F. J., Collard, H. R., Pardo, A., Raghu, G., Richeldi, L., Selman, M., Swigris, J. J., Taniguchi, H., & Wells, A. U. (2017). Idiopathic pulmonary fibrosis. Nature Reviews Disease Primers, 3, 17074.
Matchinin, A. A., Katelnikova, A. E., & Kryshen, K. L. (2019). Osobennosti otbora bronhoalveoljarnogo lavazha u laboratornyh zhivotnyh [Specific techniques of bronchoalveolar lavage collecting from laboratory animals]. Laboratory Animals for Science, (4), 37–43 (in Russian).
Mazurkevych, A. Y., Danilov, V. B., Kovpak, V. V., & Maliuk, M. O. (2014). Klitynni tekhnolohii u veterynarnii medytsyny [Cellular technologies in veterinary medicine]. Komprint, Kyiv (in Ukrainian).
Mazurkevych, A. Y., Maliuk, M. O., Kovpak, V. V., Harkevych, Y. O., & Zhuruba, V. I. (2013). Stovburovi klityny u veterynarnij medycyni. Tom 1. Eksperymentalni doslidzhennja z otrymannja, zberigannja i zastosuvannja mezenhimalnyh stovburovyh klityn [Stem cells in veterinary medicine. Volume 1. Experimental studies on receiving, storing and using mesenchymal stem cells]. Komprynt, Kyiv (in Ukrainian).
Meirelles, L. S., Fontes, A. M., Covas, D. T., & Caplan, A. I. (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine and Growth Factor Reviews, 20, 419–427.
Meloni, F., Caporali, R., Bianco, A. M., Paschetto, E., Morosini, M., Fietta, A. M., Patrizio, V., Bobbio-Pallavicini, F., Pozzi, E., & Montecucco, C. (2004). BAL cytokine profile in different interstitial lung diseases: A focus on systemic sclerosis. Sarcoidosis Vasculitis and Diffuse Lung Diseases, 21(2), 111–118.
Meyer, K. C., Raghu, G., Baughman, R. P., Brown, K. K., Costabel, U., Du Bois, R. M., Drent, M., Haslam, P., Kim, D., Nagai, S., Rottoli, P., Saltini, C., Selman, M., Strange, C., & Wood, B. (2012). An official american thoracic society clinical practice guideline: The clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. American Journal of Respiratory and Critical Care Medicine, 85(9), 1004–1014.
Meyer, K. C., Raghu, G., Baughman, R. P., Brown, K. K., Costabel, U., Du Bois, R. M., Drent, M., Haslam, P., Kim, D., Nagai, S., Rottoli, P., Saltini, C., Selman, M., Strange, C., & Wood, B. (2012). An official american thoracic society clinical practice guideline: The clinical utility of bronchoalveolarlavage cellular analysis in interstitial lung disease. American Journal of Respiratory and Critical Care Medicine, 185(9), 1004–1014.
Moodley, Y., Atienza, D., Manuelpillai, U., Samuel, C. S., Tchongue, J., Ilancheran, S., Boyd, R., & Trounson, A. (2009). Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. American Journal of Pathology, 175(1), 303–313.
Murray, P. J., & Wynn, T. A. (2011). Obstacles and opportunities for understanding macrophage polarization. Journal of Leukocyte Biology, 89(4), 557–563.
Ohshimo, S., Bonella, F., Cui, A., Beume, M., Kohno, N., Guzman, J., & Costabel, U. (2009). Significance of bronchoalveolar lavage for the diagnosis of idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 179(11), 1043–1047.
Ortiz, L. A., Gambelli, F., McBride, C., Gaupp, D., Baddoo, M., Kaminski, N., & Phinney, D. G. (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 the United States of America, 100(14), 8407–8411.
Paplińska-Goryca, M., Goryca, K., Misiukiewicz-Stępień, P., Nejman-Gryz, P., Proboszcz, M., Górska, K., Maskey-Warzęchowska, M., & Krenke, R. (2019). mRNA expression profile of bronchoalveolar lavage fluid cells from patients with idiopathic pulmonary fibrosis and sarcoidosis. European Journal of Clinical Investigation, 49(9), e13153.
Pereira, R. F., O’Hara, M. D., Laptev, A. V., Halford, K. W., Pollard, M. D., Class, R., Simon, D., Livezey, K., & Prockop, D. J. (1998). Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proceedings of the National Academy of Sciences of the United States of America, 95(3), 1142–1147.
Plumb, D. C. (2008). Plumb’s veterinary drug handbook. Sixth Edition. Blackwell Publishing.
Prasse, A., Pechkovsky, D. V., Toews, G. B., Jungraithmayr, W., Kollert, F., Goldmann, T., Vollmer, E., Müller-Quernheim, J., & Zissel, G. (2006). A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. American Journal of Respiratory and Critical Care Medicine, 173(7), 781–792.
Prockop, D. J., & Youn Oh, J. (2012). Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation. Molecular Therapy, 20(1), 14–20.
Raghu, G., Remy-Jardin, M., Myers, J. L., Richeldi, L., Ryerson, C. J., Lederer, D. J., Behr, J., Cottin, V., Danoff, S., Morell, F., Flaherty, K., Wells, A., Martinez, F., Azuma, A., Bice, T., Bouros, D., Brown, K., Collard, H., Duggal, A., Galvin, L., Inoue, Y., Gisli Jenkins, R., Johkoh, T., Kazerooni, E., Kitaichi, M., Knight, S., Mansour, G., Nicholson, A., Pipavath, S., Buendía-Roldán, I., Selman, M., Travis, W., Walsh, S., & Wilson, K. C. (2018). Diagnosis of idiopathic pulmonary fibrosis an official ATS/ERS/JRS/ALAT clinical practice guideline. American Journal of Respiratory and Critical Care Medicine, 198(5), e44–e68.
Rojas, M., Xu, J., Woods, C. R., Mora, A. L., Spears, W., Roman, J., & Brigham, K. L. (2005). Bone marrowderived mesenchymal stem cells in repair of the injured lung. American Journal of Respiratory Cell and Molecular Biology, 22(2), 145–152.
Rolandsson Enes, S., & Weiss, D. J. (2020). Cell therapy for lung disease: Current status and future prospects. Current Stem Cell Reports, 6(2), 30–39.
Saradna, A., Do, D. C., Kumar, S., Fu, Q. L., & Gao, P. (2018). Macrophage polarization and allergic asthma. Translational Research, 191, 1–14.
Selman, M., & Pardo, A. (2001). Idiopathic pulmonary fibrosis: An epithelial/fibroblastic cross-talk disorder. Respiratory Research, 3(1), 24.
Shoyaib, A., Archie, S. R., & Karamyan, V. T. (2020). Intraperitoneal route of drug administration: Should it be used in experimental animal studies? Pharmaceutical Research, 37(1), 12.
Srour, N., & Thébaud, B. (2015). Mesenchymal stromal cells in animal bleomycin pulmonary fibrosis models: A systematic review. Stem Cells Translational Medicine, 4(12), 1500–1510.
Toonkel, R. L., Hare, J. M., Matthay, M. A., & Glassberg, M. K. (2013). Mesenchymal stem cells and idiopathic pulmonary fibrosis potential for clinical testing. American Journal of Respiratory and Critical Care Medicine, 188(2), 133–140.
Tzouvelekis, A., Ntolios, P., & Bouros, D. (2013). Stem cell treatment for chronic lung diseases. Respiration, 85(3), 179–192.
Tzouvelekis, A., Toonkel, R., Karampitsakos, T., Medapalli, K., Ninou, I., Aidinis, V., Bouros, D., & Glassberg, M. K. (2018). Mesenchymal stem cells for the treatment of idiopathic pulmonary fibrosis. Frontiers in Medicint, 5(1), 142.
Uji, M., Nakada, A., & Nakamura, T. (2013). Intravenous administration of adipose-derived stromal cells does not ameliorate bleomycin-induced lung injury in rats. Open Journal of Regenerative Medicine, 2(2), 39–45.
Vasakova, M., Sterclova, M., Kolesar, L., Slavcev, A., Pohunek, P., Sulc, J., Skibova, J., & Striz, I. (2009). Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases. Scandinavian Journal of Immunology, 69(3), 268–274.
Veeraraghavan, S., Latsi, P. I., Wells, A. U., Pantelidis, P., Pantelidis, P., Nicholson, A. G., Colby, T., Haslam, P., Renzoni, E., & du Bois, R. M. (2003). BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia. European Respiratory Journal, 22(2), 239–244.
Wecht, S., & Rojas, M. (2016). Mesenchymal stem cells in the treatment of chronic lung disease. Respirology, 21(8), 1366–1375.
Weiss, D. J., English, K., Krasnodembskaya, A., Isaza-Correa, J. M., Hawthorne, I. J., & Mahon, B. P. (2019). The necrobiology of mesenchymal stromal cells affects therapeutic efficacy. Frontiers in Immunology, 4(10), 1228.
Weiss, D. J., Kolls, J. K., Ortiz, L. A., Panoskaltsis-Mortari, A., & Prockop, D. J. (2008). Stem cells and cell therapies in lung biology and lung diseases. Proceedings of the American Thoracic Society, 5, 637–667.
Wong, A. P., Chin, S., Xia, S., Garner, J., Bear, C. E., & Rossant, J. (2015). Efficient generation of functional CFTR-expressing airway epithelial cells from human pluripotent stem cells. Nature Protocols, 10(3), 363–381.
Wong, A. P., Dutly, A. E., Sacher, A., Lee, H., Hwang, D. M., Liu, M., Keshavjee, S., Hu, J., & Waddell, T. K. (2007). Targeted cell replacement with bone marrow cells for airway epithelial regeneration. Lung Cellular and Molecular Physiology, 293(3), L740-52.
Wong, A. P., Keating, A., Lu, W. Y., Duchesneau, P., Wang, X., Sacher, A., Hu, J., & Waddell, T. K. (2009). Identification of a bone marrow-derived epithelial-like population capable of repopulating injured mouse airway epithelium. Journal of Clinical Investigation, 119(2), 336–348.
Yamaguchi, K., Iwamoto, H., Mazur, W., Miura, S., Sakamoto, S., Horimasu, Y., Masuda, T., Miyamoto, S., Nakashima, T., Ohshimo, S., Fujitaka, K., Hamada, H., & Hattori, N. (2020). Reduced endogenous secretory RAGE in blood and bronchoalveolar lavage fluid is associated with poor prognosis in idiopathic pulmonary fibrosis. Respiratory Research, 21(1), 145.
Yudhawati, R., Amin, M., Rantam, F. A., Prasetya, R. R., Dewantari, J. R., Nastri, A. M., Poetranto, E., Wulandari, L., Lusida, M., Koesnowidagdo, S., Soegiarto, G., Shimizu, Y., Mori, Y., & Shimizu, K. (2020). Bone marrow-derived mesenchymal stem cells attenuate pulmonary inflammation and lung damage caused by highly pathogenic avian influenza A/H5N1 virus in BALB/c mice. BMC Infectious Diseases, 20(1), 823.
Zhang, E., Yang, Y., Zhang, J., Ding, G., Chen, S., Peng, C., Lavin, M., Yeo, A., Du, Z., & Shao, H. (2019). Efcacy of bone marrow mesenchymal stem cell transplantation in animal models of pulmonary fbrosis after exposure to bleomycin: A meta-analysis. Experimental and Therapeutic Medicine, 17(3), 2247–2255.
Zhang, L., Wang, Y., Wu, G., Xiong, W., Gu, W., & Wang, C. Y. (2018). Macrophages: Friend or foe in idiopathic pulmonary fibrosis? Respiratory Research, 19(1), 170.
Zhao, F., Zhang, Y. F., Liu, Y. G., Zhou, J. J., Li, Z. K., Wu, C. G., & Qi, H. W. (2008). Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplantation Proceedings, 40(5), 1700–1705.
Zhao, Y., Yan, Z., Liu, Y., Zhang, Y., Shi, J., Li, J., & Ji, F. (2021). Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: A systematic review and implication for clinical application. Stem Cell Research and Therapy, 12, 470.
Zhen, G., Liu, H., Gu, N., Zhang, H., Xu, Y., & Zhang, Z. (2008). Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Frontiers in Bioscience, 13(9), 3415–3422.
Zubchenko, N. I. (2016). Mizhnarodno-pravove spivrobitnytstvo derzhav u sferi zabezpechennia dobrobutu tvaryn ta yikh zakhystu vid zhorstokoho povodzhennia [International legal cooperation of states in the field of ensuring the welfare of animals and their protection from cruel treatment]. Feniks, Odesa (in Ukrainian).
How to Cite
Surtaieva, Y. V., Mazurkevich, A. Y., & Bokotko, R. R. (2022). Effects of transplanted mesenchymal stem cells on repair of the lung tissue of rats with experimental pulmonary fibrosis . Regulatory Mechanisms in Biosystems, 13(3), 308-316. Retrieved from https://medicine.dp.ua/index.php/med/article/view/828