Mesenchymal Stem Cells and Their Extracellular Vesicles: A Potential Game Changer for the COVID-19 Crisis

Abstract

Corona virus disease 2019 (COVID-19) is a global public health crisis. The high infectivity of the disease even from non-symptomatic infected patients, together with the lack of a definitive cure or preventive measures are all responsible for disease outbreak. The severity of COVID-19 seems to be mostly dependent on the patients’ own immune response. The over-activation of the immune system in an attempt to kill the virus, can cause a “cytokine storm” which in turn can induce acute respiratory distress syndrome (ARDS), as well as multi-organ damage, and ultimately may lead to death. Thus, harnessing the immunomodulatory properties of mesenchymal stem cells (MSCs) to ameliorate that cytokine-storm can indeed provide a golden key for the treatment of COVID-19 patients, especially severe cases. In fact, MSCs transplantation can improve the overall outcome of COVID-19 patients via multiple mechanisms; first through their immunomodulatory effects which will help to regulate the infected patient inflammatory response, second via promoting tissue-repair and regeneration, and third through their antifibrotic effects. All these mechanisms will interplay and intervene together to enhance lung-repair and protect various organs from any damage resulting from exaggerated immune-response. A therapeutic modality which provides all these mechanisms undoubtedly hold a strong potential to help COVID-19 patients even those with the worst condition to hopefully survive and recover.

Exploring the utility of extracellular vesicles in ameliorating viral infection-associated inflammation, cytokine storm and tissue damage

“…COVID-19 patients derived-EVs suggested that targeted drug delivery to treat pneumonia significantly reduced the cytokine storm and inflammation when compared to controls [ 32 , 37 , 38 ]. These EVs are capable of effectively inducing TH1 cellular response, giving more protection; more so than B -cell immunity [ [38] , [39] , [40] ]. The EV-induced TH1 response confers protection against airway challenge in mice models [ 37 , 41 ].…”

Mesenchymal stem/stromal cell–based therapies for COVID-19: First iteration of a living systematic review and meta-analysis

“…Mesenchymal stem/stromal cells (MSCs) were quickly viewed with significant promise to treat COVID-19 ( 11 ) and many studies were launched rapidly with several now completed and reported. MSCs are multipotent stem like cells which can be isolated from a number of adult and neonatal tissues including bone marrow, adipose, umbilical cord and placenta among the others ( 12 ).…”

Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary Success

“…The severity of the COVID-19 disease is mostly dependent on the patient responses. Over-activation of the immune system, developed in the attempt to kill the SARS-CAV-2 virus, can cause a "cytokine storm" which in turn can induce an acute respiratory distress syndrome (ARDS: [44,89]), a multi-organ damage, ultimately leading to death (miR-258, miR-266, Table 1). In COVID-19 patients, the immunomodulatory properties of MSCs ameliorate the cytokine storm by inhibiting or modulating the pathological events, especially those of severe cases [87][88][89].…”