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Aging and disease    2020, Vol. 11 Issue (5) : 1191-1201     DOI: 10.14336/AD.2020.0711
Review Article |
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.
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Abstract  

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.

Keywords Adipose Stem Cells      Mesenchymal Stem Cells      Stem Cell Therapy      COVID-19      SARS-CoV-2      Coronavirus therapy     
Corresponding Authors: Gentile Pietro   
About author:

These authors contributed equally to this work.

Just Accepted Date: 24 July 2020   Issue Date: 21 September 2020
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Gentile Pietro
Sterodimas Aris
Pizzicannella Jacopo
Calabrese Claudio
Garcovich Simone
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Gentile Pietro,Sterodimas Aris,Pizzicannella Jacopo, et al. Research progress on Mesenchymal Stem Cells (MSCs), Adipose-Derived Mesenchymal Stem Cells (AD-MSCs), Drugs, and Vaccines in Inhibiting COVID-19 Disease[J]. Aging and disease, 2020, 11(5): 1191-1201.
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http://www.aginganddisease.org/EN/10.14336/AD.2020.0711     OR
Figure 1.  CONSORT (Consolidated Standards of Reporting Trials) flow diagram.
DrugsTypeEffects TimingBiomolecular pathway/indicationsStudiesReferencesAdvantagesDisadvantages
Chloroquine
and Hydroxy-chloroquine
Antimalaric< 5 daysEarly tretament of severe COVID-19 patientsIn Vivo/ Clinical Study[14, 15]Early clinical efficacy in severe COVID-19 patientsNot specific drug against SARS-COV-2
Not autologous drug
RemdesivirAntiviral drug of nucleoside analogs-Inhibition of natural nucleoside triphosphate (NTP) to prevent virus RNA synthesis and virus replicationIn vitro/ Animal models/ Phase II and Phase III clinical trials ongoing[7, 16]Antiviral targeted against SARS-COV-2Ongoing Clinical trials
Not autologous drug Antiviral not specific against SARS-COV-2 Not autologous drug
Nucleic acid VaccinesVaccines--In Vivo/
Clinical study
NCT04283461PreventionNot yet final clinical trails results
Inactivated vaccineVaccines--Animal Models-PreventionNo yet cllinical trials
Recombinant protein vaccineVaccines--Ready for Clinical trial-PreventionNot yet final clinical trials results
Recombinant virus vector vaccineVaccines--Adenovirus vector vaccine clinical trials
Two Lentivirus vector vaccine Clinical trials
NCT04313127
NCT04299724, NCT04276896
Prevention
Prevention Prevention

Ongoing clinical trials Ongoing clinical trials Ongoing clinical trials
MSCsAntiviralmean 4.5 daysSecreting 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/
[19-22]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
AD-MSCsAntiviral/
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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