In brief

Exosome therapy could theoretically benefit patients with COVID-19, but experts caution that their safety and mechanism of action is still poorly understood.

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Call for rigor over COVID-19 exosome therapy

22 Jul 2020

Stem cell experts recognize the potential of exosomes for treating COVID-19 pneumonia, but caution that rigorous clinical testing is needed.

Most people who catch SARS-CoV-2 develop mild to moderate symptoms like shortness of breath, a dry cough and a fever, and recover without hospitalization. However, some are less fortunate—they develop severe pneumonia, a serious illness that can be deadly.

Nicknamed COVID-19 pneumonia, the condition is the result of an immune system spiraling out of control, a ‘cytokine storm’ where a cascading effect of cellular and molecular processes results in acute respiratory distress syndrome (ARDS).

A rapid uptick in studies on cell-based therapies for COVID-19 pneumonia has focused on mesenchymal stromal cells (MSCs), whose therapeutic activity is thought to be mediated by small extracellular vesicles (EVs). These MSC-EVs—also known as exosomes—are secreted by MSCs and harbor potentially therapeutic components.

“Pre-clinical studies in animal models have suggested that MSC-EVs can reduce inflammation and fibrosis in lung injury and ARDS. These studies suggest that MSC-EVs may also be effective for treating ARDS arising from COVID-19,” explained Sai-Kiang Lim, a Research Director at A*STAR’s Institute of Molecular & Cell Biology (IMCB) and co-chair of the International Society for Cellular and Gene Therapies (ISCT) Exosome Committee and founding member of the International Society for Extracellular Vesicles (ISEV).

However, while recognizing the potential of MSC-EVs, the ISEV and ISCT have published a joint statement recommending the need for rigorous clinical trials before using MSC-EVs as the standard of care to treat patients with severe COVID-19.

“The major issue with the use of MSC-EVs in COVID-19 patients is that the efficacy of MSC-EVs is not known and any use should be conducted in clinical trials under the oversight of the relevant regulatory bodies,” said Lim.

In the statement, the expert committee points out that the mechanism by which the exosomes exert their beneficial effects remains incompletely understood. Likewise, the safety and potential for adverse effects of MSC-EV therapies are still unknown.

They highlight the need to consider the source of MSCs, because the tissue and individual from which the MSCs are isolated can affect their function. In the same vein, the potency of EVs, which are thought to be responsible for the therapeutic effects of MSCs, varies depending on their source, preparation, aging and other factors.

“Both ISCT and ISEV recognize there is a strong scientific rationale for the use of MSC-EVs to treat COVID-19-induced pneumonia, but it is premature to offer MSC-EVs as a treatment for COVID-19 pneumonia at this time,” said Lim.

The A*STAR-affiliated researchers contributing to this research are from A*STAR’s Institute of Molecular & Cell Biology (IMCB).

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Börger, V., Weiss, D. J., Anderson, J. D., Borràs, F. E., Bussolati, B., et al. ISEV and ISCT statement on EVs from MSCs and other cells: considerations for potential therapeutic agents to suppress COVID-19. Cytotherapy (2020) | article

About the Researcher

Sai-Kiang Lim received her PhD degree from SUNY, Buffalo, in 1992, before completing her postdoctoral training at Columbia University first as a Cooley’s Anemia Foundation Research Fellow (1992-94) and then a Leukemia Society of America Special Fellow (1994-96). She has since led independent research groups at the National University Medical Institute, the National University of Singapore (1996-2001), the A*STAR Genome Institute of Singapore (2002-2007) and the A*STAR Institute of Medical Biology (2007-2020). Lim is currently a Principal Investigator at the A*STAR Institute of Molecular & Cell Biology, with major research interests in natural and synthetic nano lipid vesicles with specific focus on their synthesis and purification, biochemical and biophysical characterisation, and diagnostic and therapeutic applications.

This article was made for A*STAR Research by Wildtype Media Group