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Focusing on chronic lung disease

john stegmayr. photo.
John Stegmayr. Photo: Katrin Ståhl

The Lung Bioengineering and Regeneration research group is made up of about 15 researchers focusing on chronic lung disease. The group’s work includes the development of different methods to study disease models for conditions such as COPD and pulmonary fibrosis. One of the researchers, John Stegmayr, has been awarded SEK 700,000 from the Carl Tesdorpf Foundation to expand research into idiopathic pulmonary fibrosis, a severe form of lung disease.

“Idiopathic pulmonary fibrosis is an aggressive lung disease. There are two drugs that slow the progression of the disease, but no cures, and the average life expectancy after diagnosis is only 3-5 years. Lung transplantation is the final option, but this is not always possible due to the lack of donor organs or for other reasons that make the patient unable to undergo a transplant. In addition, the rejection rate is high after lung transplants compared to many other organ transplants, so new treatment strategies are needed,” says John Stegmayr.

The disease is characterised by the formation of scar tissue in the lung. The scarring is progressive and reduces the surface area available for the vital gas exchange between air in the lungs and the bloodstream. Sufferers experience shortness of breath, persistent coughing, fatigue and weight loss.

Against this background, it is crucial to gain more detailed knowledge and a better understanding of the disease. This is the aim of John Stegmayr and his colleagues, by developing functional models and platforms for studying the disease process, such as the cell populations that are involved and critical in the course of the disease.

“To date, the development of new drugs for pulmonary fibrosis has largely concentrated on a certain type of cells called fibroblasts, but this has not been very effective. So we think there are more cell types involved. Previous studies have shown there are several cell types that change in patients with idiopathic pulmonary fibrosis, but we do not yet know much about their role as the disease progresses. One way to study the cells involved in the disease is to visualise them using microscopy-based methods. This allows us to find out, for example, how they change in number, where they are located in the tissue and how they interact with their surroundings. Such information can provide important clues about their role in the disease progression.” 

What John Stegmayr and his colleagues now want to do is visualise cells in intact organs using a technique called ‘light sheet fluorescence microscopy’ instead of using conventional microscopy with specimen slices. The problem is that organs and tissues are relatively opaque to visible light. So, to visualise thicker samples with fluorescence microscopy, they must first be made transparent through a process called ‘optical clearing’. There are several ways to make biological tissue transparent, all with pros and cons, such as the time required, the use of toxic chemicals, deformation of the samples and loss of proteins.

An optical clearing method known as DISCO is most frequently used at the moment, which takes a long time and uses large quantities of toxic chemicals. This is where the money from the Carl Tesdorpf Foundation comes in. It is earmarked for a new piece of special equipment known as a SmartBatch+ system which, together with new approaches called SHIELD and eFLASH, can perform optical clearing and staining with antibodies in a quicker, more automated manner with the need for fewer toxic chemicals. Another advantage is that this method is compatible with visualisation of endogenous fluorescent proteins, which is not possible with DISCO.

“The acquired equipment will significantly increase our options for visualising cells or tissue structures in intact lungs to boost our understanding of how diseases such as IPF progress. Findings made can ultimately be factored in to the development of new treatment strategies. The equipment can also be used to prepare many organs other than lungs for 3D visualisation, so our hope is that the equipment will be useful for several other research projects at Lund University.  
 
The equipment will be located at LBIC, Lund University Bioimaging Centre, which is an open infrastructure and user environment for researchers both inside and outside Lund University.” Two new light sheet microscopes for visualisation of large biological samples, such as intact organs, are currently available via the LBIC infrastructure. John Stegmayr is employed part-time at LBIC and assists users with both optical clearing and subsequent microscopy.

About the Lung Bioengineering and Regeneration research group

The research group is led by Senior Lecturer Darcy Wagner. Lung Bioengineering and Regeneration was established in 2017 when she was appointed Wallenberg Molecular Medicine Fellow and was awarded funding from the Wallenberg Centre for Molecular Medicine (WCMM) at Lund University. Darcy Wagner has since been awarded funding from, among others, the Swedish Research Council and the ERC (European Research Council Starting Grant). The group is multinational and interdisciplinary with researchers from different academic levels and involves several medical, scientific and technical disciplines.
Link to the 
Lung Bioengineering and Regeneration research group

LBIC

LBIC (Lund University Bioimaging Centre) is a medical imaging centre at Lund University that develops and offers imaging methods to study advanced details of human morphology, cell metabolism and physiological functions in disease and health. LBIC handles a number of imaging methods in bioimaging, with an emphasis on various clinical and preclinical cameras (MRI, CT and PET), light and electron microscopy, as well as analysis and visualisation of data.

Link to Lund University Bioimaging Centre