Lung cell bank aims to help Singapore breathe easy in case of outbreak

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Dr Conrad Chan (left) of the Communicable Diseases Agency and Prof Sanjay Chotirmall, vice-dean of research at NTU LKCMedicine, at LKCMedicine's cell tissue culture lab on Apr 14.

Dr Conrad Chan (left) of the Communicable Diseases Agency and Prof Sanjay Chotirmall, vice-dean of research at NTU LKCMedicine, at LKCMedicine's cell tissue culture lab on April 14.

ST PHOTO: GIN TAY

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SINGAPORE - When Covid-19 hit, it took two years for research on how the disease affected patients with lung diseases here to be published, too late for it to have an impact on how the disease was treated, recalled Associate Professor Sanjay Chotirmall, vice-dean of research at the Nanyang Technological University’s Lee Kong Chian School of Medicine (LKCMedicine).

This sparked the idea that Singapore should have a collection of lung tissue that can inform its efforts if the Republic faces the outbreak of another disease, he said.

Such a repository could not only contribute to pandemic preparedness, but could also be used for the development of personalised treatments, research into lung diseases, drug screening and testing of new treatments, said Prof Chotirmall, who is also associate professor in molecular medicine at LKCMedicine and a clinician at Tan Tock Seng Hospital.

A national repository of advanced respiratory tissue models is now being developed by The Academic Respiratory Initiative for Pulmonary Health (TARIPH), a centre under LKCMedicine.

It will be developed over three years, during which some 200 samples will be collected from various ethnicities and age groups, including those at greater risk of infection such as children and the elderly.

A computer screen displaying airway basal stem cells in the initial expansion phase, photographed at LKCMedicine’s cell tissue culture lab.

ST PHOTO: GIN TAY

TARIPH is working in collaboration with the Programme for Research in Epidemic Preparedness and REsponse (PREPARE), a national research and development initiative under the Communicable Diseases Agency.

LKCMedicine will lead the scientific development of the repository, including the collection, processing and analysis of human lung samples.

Meanwhile PREPARE will ensure quality control and house the repository in the long term, as well as ensure it serves Singapore’s broader pandemic preparedness needs.

The specimens will eventually be available to both local and international researchers for academic purposes.

The repository for lung tissue is the first in Singapore and, according to Prof Chotirmall, is the first such national repository in an Asian country.

While there are other repositories in other countries, these mostly represent non-Asian populations, noted Prof Chotirmall.

“Disease X is likely to look different between Asians and non-Asians,” he said, referring to the term used for a hypothetical future epidemic.

Given the Republic’s multi-ethnic make-up, the repository could also assist efforts across Asia, he added.

PREPARE is funding the endeavour to the tune of $2 million, while another $2 million will come from a $10 million Open Fund-Large Collaborative Grant awarded to TARIPH in July 2024 by the National Research Foundation and administered by the National Medical Research Council.

The two will also share manpower and expertise, said Dr Conrad Chan, senior principal scientific officer at the PREPARE laboratory.

“The project’s really kicked off and we’re now actively collecting samples and banking them. The next stage is going to be looking at making sure that these samples can be grown into the lung tissue that we want,” said Dr Chan.

Following that, as part of pandemic preparedness, the tissue will be infected with different types of viruses to see how they respond, he added.

Dr Conrad Chan (left), Senior Principal Scientific Officer at the Programme for Research in Epidemic Preparedness and Response Laboratory under the Communicable Diseases Agency; and Prof Sanjay Chotirmall, NTU LKCMedicine Vice Dean (Research) and Provost’s Chair in Molecular Medicine; at cell tissue culture lab, LKCMedicine on Apr 14.

Dr Conrad Chan (left) of the Communicable Diseases Agency and Prof Sanjay Chotirmall, vice-dean of research at NTU LKCMedicine, are working to establish a national repository of advanced respiratory tissue models for lung disease research.

ST PHOTO: GIN TAY

Among the cells to be included in the repository are lung organoids, or “mini lungs” grown in a lab from human cells.

Such cells can develop into different cell types found in real lungs – such as mucus-producing cells and those that help clear out dust and germs – and arrange themselves to work in a similar way to actual lung tissue.

These allow scientists to study how lung diseases develop, how the lungs heal and how different treatments might work, without the need to test on people.

Several organoids can be grown from a single sample, which can be studied over time, making it easier to test new treatments as well as personalise them.

The repository will also include air-liquid interface cultures – airway cells, similar to those gathered during a nasal swab, grown in the lab with air on one side and nutrients on the other, like real lungs.

These will be used to study how lungs react to infections, pollution and treatments, as well as understand how illnesses like flu and coronaviruses including SARS-CoV-2, spread.

A trans epithelial electrical resistance device is used regularly to check the integrity of the air-liquid interface cell barrier.

A transepithelial electrical resistance device is regularly used to check the integrity of the air-liquid interface cell barrier.

ST PHOTO: GIN TAY

Also featured are precision-cut lung slices – extremely thin slices of real human lung tissue sampled from patients undergoing lung surgery – that can stay alive and active in the lab for extended periods.

As these keep the lung’s natural structure, including the different cell types within the organ, scientists can observe how lung tissue behaves in real time, including its response to drugs or how immune cells respond to disease.

The repository would help make the development of vaccines and therapies for diseases quicker, as well as help inform public health strategies in case of an outbreak, said Prof Chotirmall.

“You don’t have to wait for people to get infected and then see what happens to them in hospital,” said Dr Chan.

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