Stem Cells as Tools to Identify COVID-19 Treatments

June 6, 2020

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COVID-19 has had profound and far-reaching impacts, affecting the health and safety of millions of people worldwide. Scientists from different disciplines are coming together and pooling their unique skill sets and resources to better understand coronavirus infection and COVID-19 treatment. Stem cells previously have helped scientists better understand other viruses and infectious diseases, such as HIV, Zika, Hepatitis C, and Dengue fever. Today, many stem cell researchers are refocusing their attention towards combatting this global pandemic.

In a recent survey of the stem cell community, the International Society for Stem Cell Research (ISSCR) found that nearly a quarter of respondents have pivoted to work on COVID-19-related research. There is significant energy around coming together as a community to act quickly to try to identify COVID-19 treatments, joining laboratories across expertise and international borders. Some major questions in coronavirus infection revolve around which cell types can be infected, why infection responses vary greatly, and which drugs are effective and safe. Stem cells can help us address these questions, understand infection, and identify new treatments.

Pluripotent stem cells, or cells that can become any cell in the body, can be directed to become different types of cells in a laboratory, such as lung, heart, kidney, or intestinal cells. Scientists can use these cells to understand how different organs are infected by coronavirus and find drugs that might prevent or treat the infection. Stem cell models also can be derived from patients with various diseases, such as cardiovascular disease or cystic fibrosis, to understand variation in coronavirus infection and test the safety and response of different treatments in people with preexisting conditions.

Scientists are using stem cells to address coronavirus infection and COVID-19 treatment in a variety of ways. Charles Murry, MD, PhD at the University of Washington, USA, is working with virologists to dissect how cardiac disease compounds COVID-19 effects. He is using stem cells to make cardiomyocytes, the muscle cells found in the heart. He found that cardiomyocytes can be infected and killed by coronavirus, similar to lung cells, which are an established target of the virus. “This tells us that the heart disease we’re seeing in COVID-19 patients could include a component of direct cardiac infection. We are exploring other cell types in the heart and elsewhere to see how widespread susceptibility to this infection is. It would not have been possible to do these studies without stem cells.” Murry’s next step is to try to identify therapies by treating these infected stem cells with panels of drugs.

Also looking at the effect of coronavirus infection on heart cells are Christine Mummery, PhD and Richard Davis, PhD of Leiden University Medical Centre, the Netherlands. They are using stem cell-derived cardiomyocytes to evaluate the cardiac risk of drugs that are being used in tests to treat COVID-19. “Using our stem cell-derived cardiomyocytes we can see if cells derived from patients with underlying cardiac conditions respond differently to those derived from healthy individuals. We could then forewarn clinicians if this group of individuals is more “at risk” for drug side effects and might require additional monitoring.”

Lygia da Veiga Pereira, PhD, University of São Paulo, Brazil says “Stem cell-derived models will certainly speed up the process of drug development for COVID-19. Testing drugs in relevant stem cell-derived cells (lung, cardio, upper respiratory track) will allow for rapid confirmation (or rejection) of the drug, which in turn will expedite clinical trials.” In addition to efforts to identify new treatments, she is sequencing the genomes of COVID-19 patients to see if there are underlying genetic causes to the observed variation in disease response between different people. “Why do some people have full-blown disease (and die) while others are asymptomatic? There are several factors that will influence that - the state of health, age, obesity, etc., but it is reasonable to suggest that genetic variants may increase one´s resistance to the disease.” This could be revealed in her sequencing studies, which may help influence future treatments.

In a complimentary approach, Nadia Rosenthal from The Jackson Laboratory, USA is developing a large collection of stem cell models to examine the genetic component of coronavirus infection response. Researchers can use these embryonic stem cells derived from genetically diverse mice and convert them into relevant cell types. These cells can then be infected with coronavirus to assess the role of different genetic backgrounds on viral infection in different tissues. “This approach will allow us to fast-track discoveries of genetic susceptibility, leading to new diagnostic, prognostic, and therapeutic advances in the treatment of this multi-factorial disease,” says Rosenthal.

This worldwide health pandemic has mobilized a global response from the stem cell and larger biomedical research communities. Melissa Little, PhD, at Murdoch Children’s Research Institute, Australia said “This crisis will test our scientists as it will everyone, but medical research needs to be the solution.” Stem cell research has an important role to contribute to better understanding the disease and finding a treatment. But the scientific process takes time and resources, and it is important to note that there are currently no approved stem cell treatments for COVID-19. Continued support for scientific research is critical as the whole world races to find a cure. The ISSCR is committed to providing the public with current and credible scientific information and progress as it arises.

(Image: This scanning electron microscope image shows coronavirus (round gold objects) emerging from the surface of cells cultured in the lab, credit NIAID-RML).