a lung on a chip: a new tool to combat coronavirus
11 september 2024
researchers from the quadram institute working together with the uk health security agency (ukhsa) have established a human “lung-on-chip” model that recreates how sars-cov-2 infects lung cells, in a contained laboratory environment.
the model adapts current technology to allow cells that line the lungs in humans to be grown in a way that mimics physiological conditions. the cells are grown with one end based in a liquid, and the other is exposed to the air – and potentially the virus. the composition and flow of the liquid are controlled to reproduce that seen in the lung. the system also incorporates breathing-like stretching, ensuring different cells develop and interact as in the human lung.
in a study published in the journal access microbiology, the team showed how their system successfully mimics the way sars-cov-2 virus infects cells, triggering characteristic changes in the cells seen in human infections as well as recapitulating early immune response, and release of new virus particles.
taken together, these features mean this is a powerful new way for scientists to study how sars-cov-2 infects our lungs cells in the lab, to guide future clinical research and help fight back against covid.
the covid-19 pandemic prompted an unprecedented collective effort from the scientific community around the world to understand exactly how the sars-cov-2 virus caused its devastating effects.
one aspect of this was developing ways of being able to study at the cellular level exactly how the virus infects us. in mild cases, the virus infects the upper airways, but severe cases tend to be marked by infection of the lower airways, and the alveoli. these are tiny balloon-like structures in the lungs that inflate as air is brought in. oxygen passes through specialised cells that line the lungs into the blood in exchange for carbon dioxide, which is then removed. infection and damage of the alveoli is serious as it prevents this vital process, leading to respiratory failure.
an accurate model of the human alveolus, and the cells at the interface with the air, was much needed but developing a system to allow scientists to recreate it in the lab was a challenge. the standard technique of growing cells in a culture didn’t properly mimic what happens in the lung; models that better reflected the way the cells exist at the interface with air and liquid were a better mimic of the way the cells grow in alveoli. but these traditional static models don’t recreate the way the lung inflates and expands to bring in air, which in turn affects the immune response to viral infection.
to address this, prof. nathalie juge and dr tanja šuligoj from the quadram institute made use of their experience in human gut tissue models to study interactions between gut cells, mucus and the microbiome. the team worked with emulate inc. of boston, usa who specialise in developing microphysiological systems, commonly known as organ-chips. these are systems that recreate human tissues and organs on “chips” to support a range of lab-based studies, reducing the need for animal studies and potentially speeding up research into new drugs and treatments.
the quadram team adapted the alveolus lung chip that uses a combination of human alveoli lining cells and lung microvascular endothelial cells, to better reflect the way these cells form in the lung. these cells were connected to a laboratory simulation of the fluid that flows through the lung. once the cells were established, an airflow was introduced alongside mechanical flexing of the chips to copy the inflation and deflation of alveoli during breathing.
the team worked with dr simon funnell and colleagues from ukhsa to assess the suitability of the system for the study of sars-cov-2 infection in the quadram institute’s containment level 3 (cl3) facility.
there was clear evidence of virus replication in the cells in all the chips tested, with a high level of the virus detectable a day after infection and lasting until day three. this is comparable with the timeline of virus shedding in covid-19 patients. within two or three days, changes to the cells were apparent that matched those seen in other infections into the effects of covid on mammalian lung cells as well as early innate immune responses observed in naturally acquired sars-cov-2 infection in humans.
“we were pleased to be able to pivot our expertise in organ-on-chip models to contribute to the international effort to fight sars-cov-2 during the covid-19 pandemic,” said prof. juge. “
"the capacity to successfully infect lung-on-chips in quadram’s cl3 was a milestone and we are pleased to have helped transfer this expertise to ukhsa” said prof. nathalie juge. “this infection model recapitulates clinically relevant effects that can be used to combat emerging infectious respiratory diseases”.
ukhsa are continuing to develop this model to characterise virus infections with coronaviruses that cause more severe disease intending to develop a human-relevant platform to assess new drugs and treatments against past, current and future coronavirus threats such as disease x.
“ukhsa is proud to be supporting this area of research. systems such as these are becoming increasingly important in understanding the effectiveness of new drugs and play an important role in our preparation for future pandemics,” said dr kevin bewley.
the work was supported by the u.s. food and drug administration and the biotechnology and biological sciences research council (bbsrc), part of ukri.
reference: modelling sars-cov-2 infection in a human alveolus microphysiological system, tanja šuligoj, naomi coombes, catherine booth, george m. savva, kevin r. bewley, simon g. p. funnell and nathalie juge, access microbiology doi: 10.1099/acmi.0.000814.v3
image: tanja Šuligoj and catherine booth, the quadram institute.