Stem Cell Extracellular Vesicles as Anti-SARS-CoV-2 Immunomodulatory Therapeutics: A Systematic Review of Clinical and Preclinical Studies

Sarah Hamdy Ahmed; Mohamed Atef AlMoslemany; Kenneth Whitaker Witwer; Ahmed Gamal Tehamy; Nagwa El-Badri

doi:10.1007/s12015-023-10675-2

Stem Cell Extracellular Vesicles as Anti-SARS-CoV-2 Immunomodulatory Therapeutics: A Systematic Review of Clinical and Preclinical Studies

Stem Cell Rev Rep. 2024 Feb 23. doi: 10.1007/s12015-023-10675-2. Online ahead of print.

Authors

Sarah Hamdy Ahmed^{1

2}, Mohamed Atef AlMoslemany¹, Kenneth Whitaker Witwer^{3

4

5}, Ahmed Gamal Tehamy¹, Nagwa El-Badri⁶

Affiliations

¹ Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, October Gardens, Giza, 6th of October City, 12582, Egypt.
² Biotechnology/Biomolecular Chemistry Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.
³ Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Neurology and Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, October Gardens, Giza, 6th of October City, 12582, Egypt. nelbadri@zewailcity.edu.eg.

PMID: 38393666
DOI: 10.1007/s12015-023-10675-2

Abstract

Background: COVID-19 rapidly escalated into a worldwide pandemic with elevated infectivity even from asymptomatic patients. Complications can lead to severe pneumonia and acute respiratory distress syndrome (ARDS), which are the main contributors to death. Because of their regenerative and immunomodulatory capacities, stem cells and their derived extracellular vesicles (EVs) are perceived as promising therapies against severe pulmonary conditions, including those associated with COVID-19. Herein, we evaluate the safety and efficacy of stem cell EVs in treating COVID-19 and complicating pneumonia, acute lung injury, and ARDS. We also cover relevant preclinical studies to recapitulate the current progress in stem cell EV-based therapy.

Methods: Using PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science, we searched for all English-language published studies (2000-2023) that used stem cell EVs as a therapy for COVID-19, ARDS, or pneumonia. The risk of bias (ROB) was assessed for all studies.

Results: Forty-eight studies met our inclusion criteria. Various-sized EVs derived from different types of stem cells were reported as a potentially safe and effective therapy to attenuate the cytokine storm induced by COVID-19. EVs alleviated inflammation and regenerated the alveolar epithelium by decreasing apoptosis, proinflammatory cytokines, neutrophil infiltration, and M2 macrophage polarization. They also prevented fibrin production and promoted the production of anti-inflammatory cytokines and endothelial cell junction proteins.

Conclusion: Similar to their parental cells, stem cell EVs mediate lung tissue regeneration by targeting multiple pathways and thus hold promise in promoting the recovery of COVID-19 patients and improving the survival rate of severely affected patients.

Keywords: ARDS; Acute respiratory distress syndrome; COVID-19; Exosomes; Extracellular Vesicles; Pneumonia; Regenerative medicine; SARS-CoV-2; Stem cells; microRNAs.

Publication types

Review

Abstract

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