Immunomodulatory extracellular vesicles: an alternative to cell therapy for COVID-19.

Introduction: SARS-CoV-2 induces a cytokine storm and can cause inflammation, fibrosis and apoptosis in the lungs, leading to acute respiratory distress syndrome (ARDS). ARDS is the leading cause of mortality and morbidity the associated to COVID-19, and the cytokine storm is a prominent etiological factor. Mesenchymal stem cell-derived extracellular vesicles are an alternative therapy for the management of inflammatory and autoimmune conditions due to their immunosuppressive properties. The immunomodulatory and tissue regeneration capabilities of extracellular vesicles may support their application as a prospective therapy for COVID-19.Areas Covered: We explored the clinical evidence on extracellular vesicles as antiviral agents and in mitigating ARDS, and their therapeutic potential in COVID-19.Expert Opinion: Clinical trials using extracellular vesicles are registered against COVID-19 associated complications, with some evidence of safety and efficacy. Extracellular vesicles present an alternative potential for cell therapy for COVID-19 management, but further preclinical and clinical investigations are needed.

Umbilical cord: an allogenic tissue for potential treatment of COVID-19.

The COVID-19 pandemic has placed an unprecedented burden on health care systems and economies around the globe. Clinical evidences demonstrate that SARS-CoV-2 infection produces detrimental levels of pro-inflammatory cytokines and chemokines that can lead to acute respiratory distress syndrome (ARDS) and significant systemic organ damage. Currently, there is no definitive therapy for COVID-19 or associated complications, and with the hope of a safe and effective vaccine in the distant future, the search for an answer is paramount. Mesenchymal stem cells (MSCs) provide a viable option due to their immunomodulatory effects and tissue repair and regeneration abilities. Studies have demonstrated that compassionate use of MSCs can reduce symptoms associated with SARS-CoV-2 infection, eliminate fluid buildup, and act as a regenerative technique for alveolar damage; all in a safe and effective way. With multiple autologous sources available for MSCs, each with their own respective limitations, allogenic umbilical cord (UC) and/or UC-derived Wharton's jelly (WJ) seem to be best positioned source to harvest MSCs to treat COVID-19 and associated symptoms. As an allogenic source, UC is readily available, easily obtainable, and is rich in immunomodulatory and regenerative factors. In this manuscript, we reviewed the current evidences and explored the potential therapeutic use of allogenic UC and/or WJ-derived MSCs for the treatment of COVID-19. Although, preliminary preclinical and clinical studies indicate that their use is safe and potentially effective, more multi-center, randomized, controlled trials are needed to adequately assess the safety and efficacy of UC and/or WJ-derived MSCs for the treatment of COVID-19.