Research progress on Mesenchymal Stem Cells (MSCs), Adipose-Derived Mesenchymal Stem Cells (AD-MSCs), Drugs, and Vaccines in Inhibiting COVID-19 Disease
Pietro Gentile1,2,*, Aris Sterodimas3, Jacopo Pizzicannella4, Claudio Calabrese5, Simone Garcovich6
1Department of Surgical Science, University of Rome “Tor Vergata”, Rome, 00133, Italy. 2Academy of International Regenerative Medicine & Surgery Societies, Geneva, Switzerland. 3Department of Plastic and Reconstructive Surgery, Metropolitan General Hospital, Athens, Greece. 4ASL02 Lanciano-Vasto Chieti, Ss. Annunziata Hospital, Chieti, 66100, Italy. 5San Rossore Breast Unit, Pisa 56122, Italy. 6Institute of Dermatology, F. Policlinico Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy.
Mesenchymal Stem Cells (MSCs), and Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) have been used for many years in regenerative medicine for clinical and surgical applications. Additionally, recent studies reported improved respiratory activity after intravenous administration of MSCs into patients affected by coronavirus disease 2019 (COVID-19) caused by the Coronavirus 2 (SARS-CoV-2) suggesting their role as anti-viral therapy. Severe COVID-19 patients usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death in a short period after onset. Currently, there is still a lack of clinically effective drugs for such patients. The high secretory activity, the immune-modulatory effect, and the homing ability make MSCs and in particular AD-MSCs both a potential tool for the anti-viral drug-delivery in the virus microenvironment and potential cellular therapy. AD-MSCs as the most important exponent of MSCs are expected to reduce the risk of complications and death of patients due to their strong anti-inflammatory and immune-modulatory capabilities, which can improve microenvironment, promote neovascularization and enhance tissue repair capabilities. In this literature review, the role of regenerative strategies through MSCs, AD-MSCs, and adipocyte-secreted exosomal microRNAs (A-SE-miRs) as a potential antiviral therapy was reported, comparing the results found with current research progress on drugs and vaccines in COVID-19 disease.
Secreting antibacterial peptides and proteins (AMPs), indoleamine 2,3-dioxygenase (IDO), IL-17/ Activating a large number of anti-virus genes, such as IFITM gene, which can encode protein structures that prevent viruses from invading cells/ regulating the dynamic coordination of pro-inflammatory and anti-inflammatory elements of the patient’s immune system and promoting the activity of phagocytes
In Vivo/ Clinical/ In Vitro/
Early clinical efficacy in severe COVID-19 patients Autologous drug Autologous source of donor tissue Allogeneic use No svere immune reaction
Ongoing clinical trial Not specific drug against SARS-COV-2
Antiviral/ Delivery drugs
Anti-inflammatory (IL-10), immune-modulatory (TGFß-1), (HGF), (INF-γ), and pro-angiogenic activities (VEGF), (PDGF)/ Transition from inflammatory macrophage phenotype M1 to the anti-inflammatory and wound healing M2 phenotype/ Inhibition of ECM degradation through the increased binding of MMPs and secretion of TIMPs/ Delivery drug
In Vitro/ In Vivo Clinical trial ongoing
[2, 26, 27]
Early clinical efficacy in severe COVID-19 patients Autologous drug Autologous source of donor tissue Allogeneic use Potential delivery drugs No svere immune reaction Potential aereosol administration
Ongoing clinical trial Not specific drug against SARS-COV-2
Table 1 Research progress of COVID-19 therapy based on drugs, vaccines and Mesenchymal Stem Cells.
Figure 2. Graphical illustration of the anti-viral activity of SVFs and AD-MSCs via intravenous infusion and aerosol administration.
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