Umbilical cord derived stem cell (ModulatistTM) transplantation for severe chronic obstructive pulmonary disease: a report of two cases
Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is a chronic disease affecting the airway of the respiratory system. COPD cases have rapidly increased in recent years, with the disease becoming the fourth leading cause of death worldwide. Stem cell transplantation is a new approach to treat COPD. In this study we report in two cases the use of transplanted stem cells to treat COPD.
Methods: Umbilical cord derived stem cells (ModulatistTM) were used in the study. ModulatistTM was prepared according to previous published studies. Two patients with late stage COPD (stage IV) were transfused with Modulatist at a dose of 106 cells/kg. Patients were evaluated by the COPD assessment test (CAT) score as well as the Modified Medical Research Council Dyspnea Scale (mMRC) score, before and after transplantation (1, 3 and 5 months post transplantation).
Results: Results showed that ModulatistTM transplantation significantly improved sever COPD, especially after 3 months. At that time point, the two patients receiving ModulatistTM showed a significantly improvement, from late-stage of COPD (stage IV) to stage I.
Conclusion: Although these initial results suggest that ModulatistTM transplantation is a promising therapy, more clinical studies in COPD patients are warranted to evaluate efficacy.
References
Aslam, M., Baveja, R., Liang, O.D., Fernandez-Gonzalez, A., Lee, C., Mitsialis, S.A., and Kourembanas, S. (2009). Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med 180, 1122-1130.
Chen, Y.B., Lan, Y.W., Chen, L.G., Huang, T.T., Choo, K.B., Cheng, W.T., Lee, H.S., and Chong, K.Y. (2015). Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model. Cell Stress Chaperones 20, 979-989.
Gupta, N., Krasnodembskaya, A., Kapetanaki, M., Mouded, M., Tan, X., Serikov, V., and Matthay, M.A. (2012). Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax 67, 533-539.
Kochanek, K.D., Xu, J., Murphy, S.L., Minino, A.M., and Kung, H.C. (2011). Deaths: preliminary data for 2009. Natl Vital Stat Rep 59, 1-51.
Krasnodembskaya, A., Samarani, G., Song, Y., Zhuo, H., Su, X., Lee, J.W., Gupta, N., Petrini, M., and Matthay, M.A. (2012). Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol 302, L1003-1013.
Liu, H.M., Ma, L.J., Wu, J.Z., and Li, Y.G. (2015). MSCs relieve lung injury of COPD mice through promoting proliferation of endogenous lung stem cells. J Huazhong Univ Sci Technolog Med Sci 35, 828-833.
Liu, X., Fang, Q., and Kim, H. (2016). Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis. PLoS One 11, e0157099.
Minino, A.M. (2011). Death in the United States, 2009. NCHS Data Brief, 1-8.
Moodley, Y., Atienza, D., Manuelpillai, U., Samuel, C.S., Tchongue, J., Ilancheran, S., Boyd, R., and Trounson, A. (2009). Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 175, 303-313.
Ortiz, L.A., Gambelli, F., McBride, C., Gaupp, D., Baddoo, M., Kaminski, N., and Phinney, D.G. (2003). Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100, 8407-8411.
Pham, P.V., Vu, N.B., and Phan, N.K. (2016). Umbilical cord-derived stem cells (MODULATISTTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells. 2016 3, 10.
Shroff, G. (2015). Human embryonic stem cells (hESCs) in the treatment of emphysematous COPD: a case report. Clinical Case Reports 3, 632-634.
Stessuk, T., Ruiz, M.A., Greco, O.T., Bilaqui, A., Ribeiro-Paes, M.J.d.O., and Ribeiro-Paes, J.T. (2013). Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years. Revista Brasileira de Hematologia e Hemoterapia 35, 352-357.
Tan, D.B., Ong, N.E., Zimmermann, M., Price, P., and Moodley, Y.P. (2016). An evaluation of CD39 as a novel immunoregulatory mechanism invoked by COPD. Hum Immunol 77, 916-920.
Tropea, K.A., Leder, E., Aslam, M., Lau, A.N., Raiser, D.M., Lee, J.H., Balasubramaniam, V., Fredenburgh, L.E., Alex Mitsialis, S., Kourembanas, S., et al. (2012). Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 302, L829-837.
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.
Zhao, Y., Xu, A., Xu, Q., Zhao, W., Li, D., Fang, X., and Ren, Y. (2014). Bone marrow mesenchymal stem cell transplantation for treatment of emphysemic rats. Int J Clin Exp Med 7, 968-972.
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