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[2019/10/17] A Stem Cell Therapy Discovered by TVGH-NYMU May Provide a Way to Treat Idiopathic Pulmonary Fibrosis

Professor Fu from the School of Medicine, Institute of Anatomy and Cellular Biology has shed new light on pulmonary fibrosis treatment with her world-leading discovery


A Taipei Veterans General Hospital and National Yang-Ming University Research Team lead by Professor Fu has discovered that human umbilical cord mesenchymal stem cells, when transplanted into rat fibrotic lungs, are able not only to survive for an extended time, but are also an effective treatment for pulmonary fibrosis. At present, there is no medical treatment available for pulmonary fibrosis. This discovery brings hope of such a treatment and has been published in the internationally well-known journal “Theranotics”.


Professor Fu pointed out that lung tissue is damaged by many things, including smoking, air pollution, bacteria, viruses, oxidative free radicals, radiation, chemotherapy, individual genetics and many other factors. Such damage results in a reduction in the number of alveoli in the lungs, which are essential for breathing. The lost alveoli are replaced in the lungs by fibrotic tissue, and this disease process is called “pulmonary fibrosis.” Pulmonary fibrosis is not only irreversible, but results in a progressive deterioration of the lungs. As pulmonary fibrosis becomes increasingly serious, it becomes “idiopathic pulmonary fibrosis”, which eventually results in respiratory failure and then death. As a result, on a diagnosis of pulmonary fibrosis, patients have an average survival time of less than three years.


According to the World Health Organization, the number of deaths caused by lower respiratory diseases and chronic obstructive pulmonary disease are ranked third and tenth in the top ten causes of death in the world. In Taiwan, according to the Ministry of Health and Welfare, pneumonia is ranked third and lower pulmonary diseases are ranked seventh among the top ten causes of deaths. However, there is no medicine or treatment available that is able to even partially reverse the development of fibrotic lung tissue. In fact, steroids are only given to reduce discomfort in patients. In the recent years, two drugs have been approved to treat pulmonary fibrosis, these are Pirfenidone and Nintedanib. However, they are very expensive and only slow down disease progression to a limited extent. Neither is an effective treatment for pulmonary fibrosis. Therefore, identifying a treatment for chronic pulmonary fibrosis remains a major clinical issue.


Professor Fu remarked that the use of human umbilical mesenchymal stem cells does not involve any ethic issues because they are collected as a waste product after delivery of a baby. Her laboratory has discovered that human umbilical mesenchymal stem cells are easy to proliferate and that a million stem cells can be extracted from a 20cm umbilicus. Within three days of culturing, their number doubles. The team injected mesenchymal stem cells from the “Wharton’s jelly” of the human umbilicus into the lungs of rats that had induced pulmonary fibrosis. The lung damage was induced by introducing 2mg of Bleomycin into the left lung, which resulted in fibrosis. One month after the treatment with the human stem cells, they found that the injected stem cells were still alive in the lungs of the mice. While the stem cells had not differentiated into alveolar epithelial cells, they were secreting hormones and hyaluronic acid. The stem cells not only had an anti-inflammatory effect, which reduces fibroblast activation and thence fibrosis, but also induced rat macrophage activation, which generated large amounts of the enzyme MMP-9. This enzyme is able to breakdown existing collagen in the fibrotic lung. Alveolar epithelial cells in the rat lung also showed an increase in expression of TLR-4, which is known to accelerate alveolar epithelial cell repair.


Changes in pulmonary alveolar surface area of rats with pulmonary fibrosis induced by Bleomycin after being treated with human umbilical mesenchymal stem cells


Professor Fu said that, based on the group's research findings, it is clear that transplanted human umbilical mesenchymal stem cells not only stay alive in rat lungs for a long time, but are also able to effectively treat pulmonary fibrosis. These findings provide a new and promising direction for developing clinical treatments to help patients with pulmonary fibrosis. In addition, the team also found that human umbilical mesenchymal stem cells are able to survive for a long time in other rat organs, which makes them suitable for allogeneic xenografts treatment of other diseases.


The researchers who participated in this world-leading research are Professor Fu and members of her laboratory, Dr. Zhu from Kaohsiung Veterans General Hospital (KVGH) Department of Thoracic Medicine, Director Chen from Taipei Veterans General Hospital (TVGH) Trauma Center, and Dr. Tsai from Taipei Veterans General Hospital Department of Critical Care Medicine. The team is hoping to continue with the research and begin to conduct further human trials at TVGH and KVGH.


Professor Fu (right) and members of her laboratory