Scientists at A*STAR’S Genome Institute of Singapore (GIS) and Institute of Molecular Biology (IMB), have made a breakthrough discovery in the understanding of lung regeneration. Their research showed for the first time that distal airway stem cells (DASCs), a specific type of stem cells in the lungs, are involved in forming new alveoli to replace and repair damaged lung tissue, providing a firm foundation for understanding lung regeneration.
Lung damage is caused by a wide range of lung diseases including influenza infections and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Influenza infection induces acute respiratory distress syndrome (ARDS) which affects more than 150,000 patients a year in the US, with a death rate of up to 50 percent. COPD is the fifth biggest killer worldwide.
The team took a novel approach in tackling the question of lung regeneration. They cloned adult stem cells taken from three different parts of the lungs – nasal epithelial stem cells (NESCs), tracheal airway stem cells (TASCs) and distal airway stem cells (DASCs). Despite the three types of cells being nearly 99 percent genetically identical, the team made the surprising observation that only DASCs formed alveoli when cloned in vitro.
“We are the first researchers to demonstrate that adult stem cells are intrinsically committed and will only differentiate into the specific cell type they originated from. In this case, only DASCs formed alveoli because alveolar cells are found in the distal airways, not in the nasal epithelial or tracheal airway”, said Dr Wa Xian, Principal Investigator at IMB. “This is a big advancement in the understanding of adult stem cells that will encourage further research into their potential for regenerative medicine.”
Using a mouse model of influenza, the team showed that after infection, DASCs rapidly grow and migrate to influenza-damaged lung areas where they form “pods”. These “pods” mature to new alveoli which replace the alveoli that were destroyed by the infection, leading to lung regeneration.
“We have harvested these “pods” to provide insight into genes and secreted factors that likely represent key components in tissue regeneration. These secreted factors might be used as biological drugs (biologics) to enhance regeneration of the lung and airways,” said Dr Frank McKeon, Senior Group Leader of the Stem Cell and Developmental Biology at GIS.
The research was jointly led by Dr Frank McKeon from GIS and Dr Wa Xian from IMB in collaboration with scientists at the National University of Singapore (NUS), and clinicians at the Harvard Medical School and the Brigham and Women’s Hospital in Boston.
Prof Birgitte Lane, Executive Director of IMB, said, “This groundbreaking work is a fine example of collaborative research, which has brought us new insight into lung epithelial stem cells. This will have breakthrough consequences in many areas.” Dr Edison Liu, Executive Director of GIS, added, “We will continue to seek impactful collaborations and build upon this research area where there is a need for novel therapies, which will offer hope for patients suffering from respiratory diseases.”