Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination
Mehrdad Afarid and Fatemeh Sanie-Jahromi
Stem Cells Int. 2021; 2021: 6666370. Published online 2021 May 6. doi: 10.1155/2021/6666370 PMCID: PMC8103964 PMID: 34035820
Abstract
COVID-19 disease has been a global health problem since late 2019. There are many concerns about the rapid spread of this disease, and yet, there is no approved treatment for COVID-19. Several biological interventions have been under study recently to investigate efficient treatment for this viral disease. Besides, many efforts have been made to find a safe way to prevent and vaccinate people against COVID-19 disease. In severe cases, patients suffer from acute respiratory distress syndrome usually associated with an increased level of inflammatory cytokines, called a cytokine storm. It seems that reequilibrating the hyperinflammatory response of the host immune system and regeneration of damaged cells could be the main way to manage the disease. Mesenchymal stem cells (MSCs) have been recently under investigation in this regard, and the achieved clinical outcomes show promising evidence for stem cell-based therapy of COVID-19. MSCs are known for their potential for immunomodulation, defense against virus infection, and tissue regeneration. MSCs are a newly emerged platform for designing vaccines and show promising evidence in this area. In the present study, we provided a thorough research study on the most recent clinical studies based on stem cells in the treatment of COVID-19 while introducing stem cell exclusivities for use as an immune disorder or lung cell therapy and its potential application for protection and vaccination against COVID-19.
Excerpt regarding vaccines
2.7. Can Stem Cells Be Used for COVID-19 Vaccination?
Vaccination seems to be the most effective means of prevention against COVID-19 contagion. Recently, many studies have been conducted to develop the COVID-19 vaccine, and many options have been proposed, including DNA- and RNA-based engineered vaccines, but there are still limitations and warning points about the vaccines, including efficacy, tolerability, safety, and immune adaptability [84]. New approaches to vaccine development have been introduced recently, including cellular vaccine strategies which have been mostly used against cancer [85, 86]. Cellular vaccines benefit from the direct transfer of transfected host cells for in vivo production of vaccine antigens. Mesenchymal stem cells are a newfound platform for designing genetically engineered cellular vaccines that hold the promise to produce efficient and safe vehicles for enhancing the host immune response [87]. Using human-engineered mesenchymal stem cells (hu-MSCs) to produce the SARS-CoV-2 N-protein antigen is one of the promising strategies that has been reported in a recent paper of Chinese researchers as a candidate for producing the COVID-19 vaccine [88]. They showed that mesenchymal stem cells engineered to produce COVID-19 proteins could provide a new bench for effective vaccine development. In this proof of concept study, transfected allogeneic mesenchymal stem cells (carrying plasmids for SARS-CoV-2 N-protein) were applied for mice injection. Twenty days after intramuscularly or subcutaneously vaccination, blood samples from the mice were tested for detection of antibodies against N-protein using enzyme-linked immunosorbent assay (ELISA). The results of this study demonstrated that one dose of vaccination led to positive antibody production in the serum of injected mice. Moreover, the MSCs carrying the transfected gene are cleared from the bloodstream by the immune system 20 days after injection.
To be more successful in using engineered mesenchymal cells as vaccines, MSCs must be as invisible to the recipient’s immune system as possible [89]. In a recent study, human mesenchymal stem cells were genetically engineered using the MSCVneo retrovirus so that HLA-1 expression was downregulated [90]. Subsequent studies showed that the injection of these stem cells was associated with a decrease in the proliferation of mononuclear cells in animal models and human subjects [90]. Future directions in this field may include strategies to modify the transfected proteins in the stem cells by posttranslational processes such as acetylation and glycosylation. In this way, the engineered antigen becomes more like viral proteins in vivo, can simulate the host immune response much better, and increase the success rate of immune protection.
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