Potential of Human Wharton’s Jelly Mesenchymal Stem Cells (hWJMSCs) Secretome for COVID-19 Adjuvant Therapy Candidate

Abstract

SARS-CoV-2 is a virus that causes a serious lifethreatening disease known as COVID-19. Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS) and multiorgan failure requiring safe and effective therapy. The human Wharton's Jelly Mesenchymal Stem Cells (hWJMSCs) can act as an anti-inflammatory and regenerative properties due to their secretion such as cytokine, growth factor, antimicrobial, and chemokine. A natural way of producing the secreted proteins of a cell (secretome) is by culturing mesenchymal stem cells (MSCs) under starvation or serum deprivation condition. This research was performed to measure the level of Fibroblast Growth Factor-7 (FGF-7), antibacterial protein LL-37 (LL-37), interleukin 1 Receptor Antagonist (IL-1ra), respectively, in the secretome of hWJMSCs. The secretome levels at: non-starvation, 24-, 48-, and 72-hours starvation periods were measured using ELISA method. The hWJMSCs secreted levels of FGF-7, LL-37, and IL-1ra were 46.74 -72.13 pg/mL, 1.70 -4.14 ng/mL, 1.35 -8.32 pg/mL, respectively. The longer the starvation period of cells, the higher the protein levels produced. The hWJMSCs secrete FGF-7, LL-37, IL-1ra, longer starvation periods of cells will increase secretome levels. The hWJMSCs could potentially serve as adjuvant therapy for COVID-19.

hWJMSCs inhibit inflammation and apoptosis in an ARDS cell model

“… 33 , 34 , 35 Our previous study has reported that starved hWJMSCs secrete anti-inflammatory proteins, such as Interleukin 1 receptor antagonist (IL-1ra), Fibroblast Growth Factor-7 (FGF-7), and antibacterial protein LL-37. 27 We also reported that hWJMSCs secrete indolamine 2,3 dioxygenase (IDO), an anti-inflammatory protein that regulates TNF-stimulated gene-6 (TSG-6) expression and consequently ameliorates inflammation. 34 However an absence of IL-12 suppression suggested that IL-12 was not the ultimate inflammatory mediator.…”

“…This activation causes NFκB to stimulate the release pro-inflammatory cytokines, such as TNF-α, thereby resulting in inflammation ( Figure 5 ). 27 , 28 , 29

Figure 5 Proposed anti-inflammation and anti-apoptotic pathways of hWJMSCs in lung cell inflammation. LPS: lipopolysaccharide; hWJMSCs: human Wharton's jelly mesenchymal stem cells; TLR-4: Toll-like receptor-4; ACE-2: angiotensin converting enzyme-2; RAGE: receptor for advanced glycation end products; ERK1/2: extracellular signal-regulated kinase; NFκB: nuclear factor kappa B; CXCL-9: C-X-C motif chemokine ligand-9; CRP: C-reactive protein; IL-8: interleukin-8; TNF-α: tumor necrosis factor-alpha.

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Allogeneic Mesenchymal Stem Cells and Its Conditioned Medium as a Potential Adjuvant Therapy for COVID-19

“…Claudin-4, a protein implicated in the development of tight junctions, is necessary for MSCs to clear alveolar fluid. [39][40][41]…”