Yale Professor Argues That MSC-Derived Exosomes, Rather Than MSCs Themselves, May Be Superior Treatment for Cytokine Storm in COVID-19; Also Says Convalescent Plasma Contains Trillions of Exosomes with Unknown Effects and May Interfere with Antibodies

In an open-access article published online as an editorial in The Journal of Extracellular Vesicles on November 14, 2020, (https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12004), Philip Askenase (photo), MD, Professor of Medicine and Pathology, Section of Rheumatology and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, (and former 30-Year Chief of Allergy & Clinical Immunology at Yale), argues that, with regard to treatment of severe COVID-19 patients, mesenchymal stromal cell (MSC)-derived-exosomes, rather than MSCs themselves, are likely superior for therapy of the severe pneumonia and cytokine storm. The editorial is titled "COVID-19 Therapy with Mesenchymal Stromal Cells (MSC) and Convalescent Plasma Must Consider Exosome Involvement: Do the Exosomes in Convalescent Plasma Antagonize the Weak Immune Antibodies?" Dr. Askenase notes that MSCs are increasingly being used as possible treatments for COVID-19 and other serious conditions, but that their released exosomes are equivalent, safer, and more convenient. Dr. Askenase states that the exosomes themselves would thus be a better therapeutic choice versus the MSCs. In support of this assertion, he notes that many reports in the literature, and his group’s own data on treatment of spinal cord injury (PLoS One, 2018 Jan 2; 13(1):e0190358; doi: 10.1371/journal.pone.0190358) (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190358) showed that the release of exosomes from the in-vivo-systemically-administered MSCs is actually responsible for the MSC-associated beneficial effects. Furthermore, he emphasizes again that exosomes are simpler, safer, and clinically much more convenient compared to their parental MSCs. Concerning side effects in the context of COVID‐19, Dr. Askenase suggests that the known tendency of MSCs to intravascularly aggregate in the lungs, causing pulmonary dysfunction, might synergize with the pneumonia aspects of the disease.
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