Newly discovered stem cell brings COPD-research big step forward

Prof.dr. Ed Morrisey (University of Pennsylvania, VS) found a new stem cell in human lungs. 'It has a critical role in maintaining the alveoli and is altered in lung disease. Also: it does not exist in mice.' This is an important finding, because a lot of research on COPD is done in mice.

'When we discover something nobody has ever seen before, that is really exciting for me as a scientist,' says Ed Morrisey. He leads a research group in Pennsylvania (US) that partakes in the Lung Regeneration Consortium of Lung Foundation. 'You suddenly realise you are looking at something nobody understands yet. And I really enjoy exploring that, to try to make sense of it.' And exactly this happened recently.

Big discovery

Morrisey's research within the consortium focusses on differences between mice lungs and human lungs. Mice are a standard model to study COPD, but there are important differences between mice lungs and human lungs. ‘We need a realistic view on how human lungs function and how damage occurs in COPD to find new treatments.’ Morrisey explains.

For instance, mice lack respiratory bronchioles. This is tissue in the area of the human lung where the smallest airway branches interweave with the alveoli. Morrisey: 'This lack of respiratory bronchioles in mice is one of the reasons we know very little about how this specific region helps maintain alveoli and what happens in COPD.' While studying human respiratory bronchioles, his research group discovered a new stem cell. They named it RASC (Respiratory Airway Secretory Cell). 'Looking at RASCs for the first time, was one of those moments I realised this was something new. So, we felt compelled to explore it. And it proved to be a big discovery.' 

Stuck in transition

First of all, Morrisey and his group showed that RASCs are stem cells. They can develop into a specific type of cell that lines the alveoli (alveolar epithelial cells type 2). Also, they discovered how to control this. 'We found the cell's 'switch' that turned RASCs into these epithelial cells. And this only worked in one direction: the alveolar epithelial cells could not be turned back into RASCs.' Also, they noticed that many RASCs in human samples with COPD no longer developed into these epithelial cells. 'They got stuck in transition.' 
To confirm this was linked to lung damage, Morrisey reached out to a different research group that studies lung damage in ferrets. Morrisey: 'Ferrets do have respiratory bronchioles. RASCs in ferrets exposed to cigarette smoke also showed this strange behaviour and got stuck.' The researchers showed that in COPD lungs, many pathways in the cells, including immune signalling, were disrupted in RASCs as well as in epithelial cells. The results were published March 30. in the renowned scientific magazine Nature.

New ways to treat COPD

But what does this mean for people suffering from COPD? Morrisey: 'It proves that RASCs have a critical role in maintaining the alveoli and are altered in chronic lung disease.’ This is essential knowledge. Since Morrisey also found several disrupted pathways in the cell, in the future he can explore whether any of these play a role in development of COPD. ‘We hope that these studies will lead to new ways to treat COPD.'

Sense of urgency

Morrisey is enthusiastic about working in the Lung Regeneration Consortium. The consortium has broken down the large question of 'how does COPD work?' into smaller questions. And has several groups of top scientists work together on each question. An important, albeit not very tangible result, Morrisey says, is the worldwide change in attitude towards COPD-research the Consortium contributes to. 'A sense of urgency has finally arisen. This is supporting those who suffer from COPD. And it leverages our work to open up new scientific doors.'

Speeding up the process

Furthermore, working parallel on research questions and discussing work in early stages speeds up the scientific process. 'For instance, there was an experiment I wanted to do, but I learned somebody else tried this and it didn't work. And often when we combine results, there is new value to what we see. Also, we exchange experiences about cutting edge lab techniques.'

Due to these lab techniques, the consortium was able to take big steps forward in recent years. To illustrate, Morrisey reports on Single Cell Genomics, 'a revolutionary technique'. It allows scientists to analyse huge amounts of cells at the same time. They can see what happens in individual cells, which ones differ and what changes in cell biochemistry cause this. 'We used this in the study of human respiratory bronchioles. RASCs stood out, and this led to their discovery.' Organoids, or mini-organs, have the same importance. 'Five years ago, these were basically non-existent. Now organoids make it possible to culture and study cells on a molecular level. This enabled us to explore the role of RASCs.’

The techniques and the data they generate, help researchers like Morrisey to identify molecules that can control the mechanisms behind lung damage and repair. ‘And after that, finding solutions for people suffering of COPD is just a race to the finish.'

Text: Karin Postelmans