Newcells hiPSC lung models; Valuable tools in understanding health impacts of air pollution

In 2014, the World Health Organisation (WHO) estimated that air pollution leads to 7 million deaths per year. This figure is more than the number of deaths from AIDS, malaria and tuberculosis combined and makes air pollution the world’s most significant single environmental health risk.1  

Nearly 2 million of these deaths are due to the effect of air pollution on the lungs, and 43% of all lung disease and lung cancer deaths are attributable to air pollution.1  

The conducting airways of the lungs are regularly exposed to the damaging effects of pollutants, gasses and nanoparticles present in the atmosphere. Current assessments of the impacts of air pollutants on human health are based on epidemiological studies, animal models and immortalised cell lines. However, given that epidemiological studies alone are rarely able to prove cause, the many differences between animal and human lung physiology, and cell lines poorly represent human biology, there is an unmet need for human in-vitro lung model tools. 

Newcells Biotech has been developing functional lung organoids derived from human induced pluripotent stem cells (hiPSC). These organoids have tight junctions and a structured pseudostratified epithelium, strikingly similar to in vivo airways. We have observed functional basal cells, goblet cells, club cells, ciliated cells and a mucus layer on the apical side with beating cilia.  

In collaboration with the Harwell based Public Health England laboratory, we have tested our organoids for inhalation toxicology with cigarette smoke condensate, cerium nanoparticles, busulfan and other compounds over 24 hours and assessed the activation of toxicological pathways using qPCR. These results pave the way for a more extensive assessment of the response of the toxicological pathways in the lung to varying concentrations of chemicals using RNA sequencing.  

Long-term and even short-term exposure to air pollution has already been shown to have the following effects2: 

Exacerbation of existing conditions  

Air pollution can have adverse effects on the respiratory system and exacerbate lung conditions such as Chronic Obstructive Pulmonary Disease (COPD) and asthma.  

Air pollutants such as particulate materials from fossil fuel combustion can cause inflammation in the lung and further impair the reduced pulmonary function in COPD patients.3 When exposed to particulate pollution, patients with COPD usually have more emergency room visits and more hospital admissions.4 In 2016, ambient air pollution was estimated to cause about 25% of COPD deaths.5 

Air pollution can also affect asthma prevalence, onset, symptoms, and reaction to treatment. Exposure during infancy to NO2 increases the risk of childhood asthma. Increased outdoor air pollution levels have also been associated with more frequent use of rescue inhalers in patients with asthma.6 

Lung development  

Children are more vulnerable to breathing in polluted air than adults and pollution is known to restrict lung development in children.  

A recent study concluded that in children, diesel-dominated air pollution reduces lung capacity by 5%. This was linked to exposure to NO2 and other nitrogen oxides.7 Exposure to air pollution has also been associated with prematurity, low birth weight and even mental illness in children.8,9  

Cancer 

Lung cancer is one of the most common cancers in urban populations.6 Diesel engine exhaust, outdoor air pollution and particulate matter have all been classified by the WHO as carcinogenic to humans.10 

Data from the Global Burden of Disease Project indicated that in 2010, there were 223,000 lung cancer deaths resulting from air pollution. Data from 2016 showed that worldwide, ambient air pollution is estimated to cause about 16% of lung cancer deaths.5 

 

Iresponse to these risks, in 2016, the UK government called for Clean Air Zones (CAZ) in city centres in an attempt to “improve the urban environment to support public health and the local economy, making cities more attractive places to live, work, do business and spend leisure time”.11 Under the plans, CAZ will be introduced in Birmingham, Leeds, Nottingham, Derby and Southampton by 2020. Similar strategies have since been proposed in other city centres, including Newcells Biotechs’ hometown Newcastle-upon-Tyne. CAZ will see the most polluting vehicles, such as old buses, taxis, coaches and lorries, discouraged from entering the zone through charges.  

Despite this, Asthma UK suggest that as the plans don’t include cars, it is highly unlikely that they will significantly improve air quality and health.12 In addition, Low Emission Zones implemented in London have improved air quality, but there is no evidence that they have helped improve children’s respiratory health. 7 

It is therefore essential that we continue to increase our understanding of how air pollution affects the human body and in particular the lungs. Newcells’ lung organoids have the potential to be valuable to tool to researchers in this field.  

References 

  1. World Health Organisation. 7 million premature deaths annually linked to air pollution. Available from: https://www.who.int/mediacentre/news/releases/2014/air-pollution/en/ [Accessed 25 Jul 2019] 
  2. GOV.UKHealth matters: air pollution. Available from: https://www.gov.uk/government/publications/health-matters-air-pollution/health-matters-air-pollution [Accessed 25 Jul 2019] 
  3. Abbey, D. E. Burchette, R. J. Knutsen, S. F. McDonnel, W. F. Lebowitz, M. D. Enright, P. L. Long-term Particulate and Other Air Pollutants and Lung Function in NonsmokersAmerican Journal of Respiratory and Critical Care Medicine. 1998. 158(1)289-98. Available from: https://doi.org/10.1164/ajrccm.158.1.9710101    
  4. U.S. Environmental Protection Agency. Air quality index. Research Triangle Park. NC: 2009. Available from: http://www.airnow.gov [Accessed 26 Jul 2019] 
  5. World Health OrganisationMortality and burden of disease from ambient air pollution. Available from: https://www.who.int/gho/phe/outdoor_air_pollution/burden_text/en/ [Accessed 29 ul 2019]  
  6. Jiang, X-Q. Mei, X-D. Feng, D. Air pollution and chronic airway diseases: what should people know and do? Journal of Thoracic Disease. 2016. 8(1): E31–E40. Available from: http://jtd.amegroups.com/article/view/5951/6192 [Accessed 26 Jul 2019] 
  7. Mudway, I.S. Dundas, I. Wood, H.E. Marlin, N. Jamaludin, J.B. Bremner, S.A. Cross, LGrieve, A. Nanzer, A. Barratt, B.M. Beevers, S. Dajnak, D. Fuller, G.W. Font, A. Colligan, G. Sheikh, A. Walton, R. Grigg, J. Kelly, F.J. Lee, T.H. Griffiths, C.JImpact of London’s low emission zone on air quality and children’s respiratory health: a sequential annual cross-sectional study. Lancet Public Health. 2019. 4(1):e28-e40. Available from: https://doi.org/10.1016/S2468-2667(18)30202-0  
  8. Liu, Y. Xu, J. Chen, D. Sun, P. Ma, X. The association between air pollution and preterm birth and low birth weight in Guangdong, ChinaBMC Public Health. 2019. 19: 3. Available from: https://doi.org/10.1186/s12889-018-6307-7  
  9. Oudin, A. Bråbäck, L. Oudin Åström, D. Strömgren, M. Forsberg, B. Association between neighbourhood air pollution concentrations and dispensed medication for psychiatric disorders in a large longitudinal cohort of Swedish children and adolescentsBMJ Open. 2016. 6: e010004. Available from: http://dx.doi.org/10.1136/bmjopen-2015-010004  
  10. GOV.UK. Understanding the impact of particulate air pollution. Available from: https://publichealthmatters.blog.gov.uk/2015/11/03/understanding-the-impact-of-particulate-air-pollution/ [Accessed 29 Jul 2019] 
  11. GOV.UKAir quality: clean air zone framework for England. Available from: https://www.gov.uk/government/publications/air-quality-clean-air-zone-framework-for-england [Accessed 29 Jul 2019] 
  12. Asthma UK. Implementation of Clean Air Zones in England. Available from: https://www.asthma.org.uk/globalassets/get-involved/external-affairs-campaigns/our-work-with-governments/consultation-responses/clean-air-zone-framework-consultation.pdf [Accessed 29 Jul 2019]  
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