Abstract
Considering the high impact that severe Coronavirus disease 2019 (COVID-19) cases still pose on public health and their complex pharmacological management, the search for new therapeutic alternatives is essential. Mesenchymal stromal cells (MSCs) could be promising candidates as they present important immunomodulatory and anti-inflammatory properties that can combat the acute severe respiratory distress syndrome (ARDS) and the cytokine storm occurring in COVID-19, two processes that are mainly driven by an immunological misbalance. In this review, we provide a comprehensive overview of the intricate inflammatory process derived from the immune dysregulation that occurs in COVID-19, discussing the potential that the cytokines and growth factors that constitute the MSC-derived secretome present to treat the disease. Moreover, we revise the latest clinical progress made in the field, discussing the most important findings of the clinical trials conducted to date, which follow 2 different approaches: MSC-based cell therapy or the administration of the secretome by itself, as a cell-free therapy.
【저자키워드】 severe acute respiratory syndrome coronavirus 2, High dose, Respiratory failure, acute respiratory distress syndrome, Mesenchymal stromal cells, nitric oxide, multisystem inflammatory syndrome in children, Neutrophil extracellular traps, body weight, interleukin-10, angiotensin converting enzyme 2, microRNA, intensive care unit, human leukocyte antigen, interleukin-6, interleukin-1, C-reactive protein, Extracellular vesicles, Galectin-9, lactate dehydrogenase, dendritic cells, interleukin 8, Food and Drug Administration, interleukin, tumor necrosis factor, Regulatory T cell, Bronchoalveolar lavage fluid, low dose, inhalation, Aspartate aminotransferase, galectin-3, Allogeneic, nanovesicles, Toll-like receptors, hepatocyte growth factor, lipopolysaccharide, reactive oxygen species, interleukin-1β, programmed cell death protein 1, Invasive mechanical ventilation, administration, intravenous, major histocompatibility complex, mitogen-activated protein kinase, cluster of differentiation, alanine aminotransferase, transforming growth factor, cyclic adenosine monophosphate, prostaglandin E2, SARS-CoV-2severe acute respiratory syndrome coronavirus 2, ICUIntensive Care Unit, ARDSacute respiratory distress syndrome, TNFTumor Necrosis Factor, FDAFood and Drug Administration, coronavirus disease of 2019, CRPC-reactive protein, IDOIndoleamine 2, Indoleamine 2, NONitric Oxide, LDHlactate dehydrogenase, nuclear factor-kappa B, HLAHuman leukocyte antigen, ACE2angiotensin converting enzyme 2, Interleukin-4, IL-6interleukin-6, IFN-γinterferon-γ, interferon-γ, IL-1βinterleukin-1β, IL-4interleukin-4, LPSlipopolysaccharide, MAPKmitogen-activated protein kinase, MHCMajor Histocompatibility Complex, TNF-αtumor necrosis factor-α, tumor necrosis factor-α, EVsextracellular vesicles, FGFfibroblast growth factor, fibroblast growth factor, GM-CSFgranulocyte macrophage-colony stimulating factor, granulocyte macrophage-colony stimulating factor, HGFhepatocyte growth factor, NIHNational Institutes of Health, National Institutes of Health, PGE2prostaglandin E2, VEGFvascular endothelial growth factor, vascular endothelial growth factor, ROSreactive oxygen species, IL-7Interleukin 7, Interleukin 7, IL-8interleukin 8, COVID-19Coronavirus disease of 2019, MSCsmesenchymal stromal cells, IL-2interleukin-2, interleukin-2, IL-10interleukin-10, IP-10inducible protein 10, inducible protein 10, MCP-1monocyte chemoattractant protein-1, monocyte chemoattractant protein-1, ASTaspartate aminotransferase, ALTalanine aminotransferase, IL-1interleukin-1, Sprotein spike, protein spike, AT2type 2 alveolar cells of the lungs, type 2 alveolar cells of the lungs, TGFtransforming growth factor, NKnatural, natural, DCsdendritic cells, BALFbronchoalveolar lavage fluid, G-CSFgranulocyte colony-stimulating factor, granulocyte colony-stimulating factor, NETsNeutrophil Extracellular Traps, RFrespiratory failure, CDcluster of differentiation, TLRtoll-like receptors, 3-dioxygenase, STAT3signal transducer activators of transcription-3, signal transducer activators of transcription-3, IL1RaInterleukin-1 receptor antagonist, Interleukin-1 receptor antagonist, TSG-6TNF-α-stimulating gene 6, TNF-α-stimulating gene 6, NF-κBnuclear factor-kappa B, IL1-αinterleukin 1-α, interleukin 1-α, IL1-βinterleukin 1-β, interleukin 1-β, IL-7interleukin-7, interleukin-7, IL-9interleukin, miRNAmicroRNA, TGF-β1transforming growth factor-β1, transforming growth factor-β1, KGFkeratinocyte growth factor, keratinocyte growth factor, Fas-LFas ligands, Fas ligands, PD-1programmed cell death protein 1, PD-L1programmed death ligand-1, programmed death ligand-1, cAMPcyclic adenosine monophosphate, IL-2RIL-2 receptor, IL-2 receptor, FOXP3 +forkhead box P3 +, forkhead box P3 +, Tregregulatory T cell, Gal-1galectin-1, galectin-1, Gal-3galectin-3, Gal-9galectin-9, GvHDacute graft-versus-host disease, acute graft-versus-host disease, UC-MSCsumbilical cord derived MSCs, umbilical cord derived MSCs, PLX-PADplacental expanded, placental expanded, MIS-Cmultisystem inflammatory syndrome in children, BM-MSCsbone marrow derived MSCs, bone marrow derived MSCs, AT-MSCsAdipose Tissue derived Mesenchymal Stromal Cells, Adipose Tissue derived Mesenchymal Stromal Cells, Allo-MSCsAllogeneic Mesenchymal Stromal Cells, Allogeneic Mesenchymal Stromal Cells, WJ-MSCsWharton’s Jelly–derived Mesenchymal Stromal Cells, Wharton’s Jelly–derived Mesenchymal Stromal Cells, HB-AT-MSCsHope Biosciences autologous adipose-derived mesenchymal stromal cells, Hope Biosciences autologous adipose-derived mesenchymal stromal cells, DW-MSCsDaewoong Pharmaceutical’s Mesenchymal Stromal Cells, Daewoong Pharmaceutical’s Mesenchymal Stromal Cells, DSCsPlacenta-derived decidua stromal cells, Placenta-derived decidua stromal cells, PL-MSCsPlacental-derived Mesenchymal Stromal Cells, MB-MSCs, Menstrual blood-derived Mesenchymal Stromal Cells, Placental-derived Mesenchymal Stromal Cells, IVintravenous, LdLow dose, HdHigh dose, IMVInvasive mechanical ventilation, admadministration, bwBody weight, Alloallogeneic, INHinhalation, NVsnanovesicles, 【초록키워드】 COVID-19, public health, Coronavirus disease 2019, ARDS, clinical trial, therapy, MSCs, cytokine, immunomodulatory, therapeutic, Mesenchymal stromal cell, immune dysregulation, Secretome, complex, syndrome, pharmacological management, candidate, Severe respiratory distress, treat, growth factor, inflammatory process, immunological, Cell, the disease, conducted, occur, driven by, anti-inflammatory property, the cytokine storm, 【제목키워드】 therapy, severe COVID-19, clinical, management,