Copyright ©The Author(s) 2020.
World J Stem Cells. Aug 26, 2020; 12(8): 731-751
Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.731
Table 1 Most common therapeutic compounds used for the treatment of coronavirus disease-19
AgentsMechanism of actionApproval
Antimalarial agentChloroquine/hydroxychloroquineInhibition of RNA-dependent RNA polymerase, Increase of endosomal and lysosomal pHFDA approved (under investigation for COVID-19)
Antiviral agentRibavirinInducing mutations in RNA-dependent replication in RNA viruses, stop viral RNA synthesisFDA approved (under investigation for COVID-19)
NelfinavirInhibitor of viral proteasesFDA approved (under investigation for COVID-19)
RemdesivirInhibition of viral RNA-dependent RNA polymerase and proofreadingFDA approved (for COVID-19)
Anti-rheumatic agentBaricitinib/ruxolitinibJAK inhibitor/suppression of immune cellsClinical Trial phase III
Monoclonal antibodyTocilizumabHumanized monoclonal antibody against the interleukin-6 receptor (IL-6R) and IL-6FDA approved (under investigation for COVID-19)
AnakinraHumanized monoclonal antibody against IL-1RFDA approved (under investigation for COVID-19)
VaccinationAd5-nCoVRecombinant adenovirus type 5Clinical Trials Phase II
ChAdOx1 nCoV-19Adenovirus vectorClinical Trials Phase I-II
INO-4800DNA plasmid delivered by electroporationClinical Trials Phase I-II
NVX-CoV2373Recombinant S protein of SARS-CoV-2Clinical Trial Phase I
LV-SMENP-DCMinigene vaccination in combination with modified DCsClinical Trial Phase I
Human antibodiesConvalescent plasmaPlasma enriched with antibodies specific to SARS-CoV-2, derived from convalescent patientsClinical Trials Phase I
Stem cellsMSCs and derivatives (exosomes)Suppression of the overactivated immune response through cell-cell contact and secretion of soluble factorsClinical Trials Phase I
Table 2 Immunomodulation mechanisms of mesenchymal stromal cells
Implicated biomoleculesMechanism of actionImplicated immune cellsResult
Cell-cell contactFas/fas ligandFas/fas ligand death signaling pathway/FADD/caspases activation or TRAIL signaling pathwayMacrophages, DCs, T and B cellsApoptosis
PD-L1/ PD-1PD-L1 induced death through binding with the inhibitory checkpoint protein PD-1T and B cellsReducing cell proliferation, reducing apoptosis of T reg
HLA-G/LIRB2 (ILT4/CD85d) and KIR2DL4 (CD158d)HLA-G/LIRB2 interaction /phosphorylation of TIMS/SHP phosphatases activation/ MAPK downregulationDCs, NK cells and T cellsInhibition of cellular proliferation
Soluble factorsPGE2PGE2/cAMP production/ downregulation of IL-2, IL-2R expression. PGE2/ downregulation of PtdIn/ suppression of T cell receptor signalingMacrophages, DCs, T and B cellsM2 macrophages switching; Prevention of DCs maturation, T and B cell inactivation
IDOIDO blocks the conversion of tryptophan to kyneurenin/in combination with TGF-β1 and HGFDCs NK cells, T and B cellsG0/G1 cell cycle arrest
NONO/suppression of STAT5 phosphorylationMacrophages, T and B cellsInhibition of cellular proliferation
GalectinsCrosslinking with TCR/clustering preventionT and B cellsInhibition of T and B cell proliferation
Soluble HLA-G isoformsSimilar interaction mechanism as membrane bound HLA-G isoformsDCs, NK cells and T cellsInhibition of cellular proliferation
ΕVsmiR-21-5p, miR-142-3p, miR-223-3p, and miR-126-3pInteraction with JAG1, PDCD4, IL-12p35, downregulation of IL-6 expressionDCsInhibition of DC maturation
miR-145, miR-146 and miR-155Suppression of TRAF6 and IL-1 IRAK1 expression/down-regulation of NF-κB p65 phosphorylation/decrease in TNF- α, ΙL-1β and IL-6 productionMacrophages, T cellsInactivation of M1 macrophages; Switching from Th1 to Th2 responses
Table 3 Clinical trials associated with the use of mesenchymal stromal cells in coronavirus disease-19
NCT numberTitleStatusMSCs originRoute of infusion
NCT04252118Mesenchymal stem cell treatment for pneumonia patients infected with COVID-19RecruitingNot specifiedIntravenously
NCT04313322Treatment of COVID-19 patients using Wharton's Jelly-mesenchymal stem cellsRecruitingWharton’s Jelly MSCsIntravenously
NCT04336254Safety and efficacy study of allogeneic human dental pulp mesenchymal stem cells to treat severe COVID-19 patientsRecruitingAllogeneic human dental pulp stem cellsIntravenously
NCT04288102Treatment with mesenchymal stem cells for severe COVID-19RecruitingNot specifiedIntravenously
NCT04346368Bone marrow-derived mesenchymal stem cell treatment for severe patients with COVID-19Not yet recruitingBM-MSCsIntravenously
NCT04366323Clinical trial to assess the safety and efficacy of intravenous administration of allogeneic adult mesenchymal stem cells of expanded adipose tissue in patients with severe pneumonia due to COVID-19Not yet recruitingAllogeneic and expanded adipose tissue-derived MSCsIntravenously
NCT04276987A pilot clinical study on inhalation of mesenchymal stem cells exosomes treating severe novel coronavirus pneumoniaNot yet recruitingMSCs-derived exosomes5 times aerosol inhalation of MSCs derived exosomes
NCT04269525Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) treatment for the 2019-novel coronavirus (nCOV) pneumoniaRecruitingUC-MSCsIntravenously
NCT04348461Battle against COVID-19 using mesenchymal stromal cellsNot yet recruitingAllogeneic and expanded adipose tissue-derived MSCsIntravenously
NCT03042143Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) (COVID-19)RecruitingHuman umbilical cord derived CD362 enriched MSCsIntravenously
NCT04333368Cell therapy using umbilical cord-derived mesenchymal stromal cells in SARS-CoV-2-related ARDSRecruitingUmbilical cord Wharton's jelly-derived humanIntravenously
NCT04352803Adipose mesenchymal cells for abatement of SARS-CoV-2 respiratory compromise in COVID-19 diseaseNot yet recruitingAutologous adipose MSC'sIntravenously