Lung and heart stem cell research paves way for new COVID-19 treatments

Melbourne researchers have used heart and lung stem cells infected with the virus that causes COVID-19 to better understand how the disease impacts different organs, paving the way for more targeted treatments.

The research, co-led by Murdoch Children’s Research Institute and the Peter Doherty Institute for Infection and Immunity (Doherty Institute), found the responses to SARS-CoV-2 varied significantly depending on the cell type, allowing the team to identify effective anti-viral drugs to treat infection in heart and lung cells. The findings were published in the 10^th anniversary edition of Stem Cell Reports. 

Murdoch Children’s Associate Professor David Elliott, also a principal investigator at The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), said discovering that COVID-19 triggered variable cellular responses in different organs would provide new insights into treatment strategies.

“To further our knowledge on the impact of SARS-CoV-2 on different organs, we engineered human stem cells in the lab into lung and heart cells and infected with them with the virus,” he said.

“We found the heart and lungs exhibit distinct antiviral and toxicity profiles that could inform better COVID-19 therapies and treat its complications.

“Our findings highlight the importance of using several cell types for the evaluation of antiviral drugs to determine the best drug combinations for effective treatment of a virus that affects multiple organ systems.”

The Royal Melbourne Hospital and University of Melbourne Professor Kanta Subbarao, Virologist and Director of the WHO Collaborating Centre for Reference and Research on Influenza at the Doherty Institute, said while SARS-CoV-2 primarily infected the respiratory tract, lung and cardiac complications occur in severe cases of COVID-19.

Cardiac complications are observed in up to 78 per cent of recovered COVID-19 patients and ongoing myocardial inflammation in 60 per cent of patients. 

“Although COVID-19 vaccines are highly effective in preventing severe illness and death, antiviral compounds are required for the treatment of COVID-19, particularly with the emergence of variant viruses that evade immunity,” Professor Subbarao said.

“To date, only a handful of drugs have been approved for use in hospitalised COVID-19 patients and more are needed.” 

The study also looked at approved drugs for treating COVID-19, including Remdesivir and Molnupiravir, with some found to be more effective than others at treating infection in lung and heart stem cells. It identified Alectinib and SPHINX31 as promising antivirals for SARS-CoV-2 in both heart and lung cells.

“We have provided valuable insights into virus-host interactions in tissues that are significantly affected in COVID-19, with implications that will further therapeutic options,” Professor Subbarao said.

Researchers from Monash University, The University of Sydney, The Walter and Eliza Hall Institute of Medical Research, the University of Melbourne and The Royal Children's Hospital also contributed to the findings.

Publication: Rajeev Rudraraju, Matthew J. Gartner, Jessica A. Neil, Elizabeth S. Stout, Joseph Chen, Elise J. Needham, Michael See, Charley Mackenzie-Kludas, Leo Yi Yang Lee, Mingyang Wang, Hayley Pointer, Kathy Karavendzas, Dad Abu-Bonsrah, Damien Drew, Yu Bo Yang Sun, Jia Ping Tan, Guizhi Sun, Abbas Salavaty, Natalie Charitakis, Hieu T. Nim, Peter D Currie, Wai-Hong Tham, Enzo Porrello, Jose M. Polo, Sean J. Humphrey, Mirana Ramialison, David A. Elliott and Kanta Subbarao, ‘Parallel use of human stem cell lung and heart models provide insights for SARSCoV-2 treatment,’ Stem Cell Reports. DOI: 10.1016/j.stemcr.2023.05.007

*The content of this communication is the sole responsibility of the Murdoch Children’s and does not reflect the views of the NHMRC.

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Dr Beth Stout, Murdoch Children’s Research Officer, Heart Disease

Dr Jessica Neil, Doherty Institute Research Officer 

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About Murdoch Children’s Research Institute

Murdoch Children's Research Institute is the largest child health research institute in Australia committed to making discoveries and developing treatments to improve child and adolescent health in Australia and around the world. They are pioneering new treatments, trialling better vaccines and improving ways of diagnosing and helping sick babies, children and adolescents. It is one of the only research institutes in Australia to offer genetic testing to find answers for families of children with previously undiagnosed conditions.

About the Peter Doherty Institute for Infection and Immunity

Finding solutions to prevent, treat and cure infectious diseases and understanding the complexities of the immune system requires innovative approaches and concentrated effort. This is why The University of Melbourne – a world leader in education, teaching and research excellence – and The Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, treatment and medical research – have partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally.

Funding

This work was supported by The Medical Research Future Fund (MRF9200007; K.S., E.R.P., J.M.P., D.A.E.) and the Victorian State Government (Victorian State Government (DJPR/COVID-19; K.S., M.R., E.R.P., J.P., D.A.E.) and COVID-19 Victorian Consortium (KS). E.R.P., M.R., D.A.E. are supported by The Novo Nordisk Foundation Center for Stem Cell Medicine (Grant NNF21CC0073729), The Stafford Fox Medical Research Foundation and The Royal Children’s Hospital Foundation. Fellowship support provided by National Health and Medical Research Council of Australia (E.R.P. and K.S.). Murdoch Children’s is supported by the Victorian Government’s Operational Infrastructure Support Program. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.