Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses

Abstract

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton’s jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

Osteogenic potential of a 3D printed silver nanoparticle-based electroactive scaffold for bone tissue engineering using human Wharton's jelly mesenchymal stem cells

“…2(d)). Even though ISCT mentioned that ≥95% of MSCs should express CD105, there are several studies demonstrating that expression of the CD105 marker by MSCs could be varied, such as 88.1%, 39 90.76%, 36 92.94%, 51 and 94.54%, 52 depending on the isolated methods, cell source, culture time in vitro , and differentiation status. 36,53 Thus, the isolated cells still comply with the ISCT's criteria even though the cell population that emits CD105 does not reach 95%.…”

Human embryonic stem cell‐derived mesenchymal stem cell secretome reverts silica‐induced airway epithelial cell injury by regulating Bmi1 signaling

“…Importantly, intravenous administration of IMRCs also have shown effectiveness in treatment of human COVID-19 patients in a clinical trial. 18 Together with that up to 80% of the therapeutic effects of MSCs are regulated by paracrine factors, 22 these findings suggest that the secretome of MSC culture medium (CM) has great therapeutical potencies for treatments of many diseases including COVID-19 infection, 23 wound healing 24 and liver fibrosis, 25 which opens a new avenue for developing on-shelf cell-free agents of MSC-based therapeutics. 26 In light of aforementioned studies, we thus hypothesized that hESC-MSC-IMRCs and their secretome also possess therapeutic potencies in treatment of silicosis, through a mechanism by regulating Bmi1 signaling and restoring the plasticity of silica-induced exhaustion of epithelial stem cells.…”

“…Importantly, intravenous administration of IMRCs also have shown effectiveness in treatment of human COVID‐19 patients in a clinical trial 18 . Together with that up to 80% of the therapeutic effects of MSCs are regulated by paracrine factors, 22 these findings suggest that the secretome of MSC culture medium (CM) has great therapeutical potencies for treatments of many diseases including COVID‐19 infection, 23 wound healing 24 and liver fibrosis, 25 which opens a new avenue for developing on‐shelf cell‐free agents of MSC‐based therapeutics 26 …”

Understanding the Role of Mesenchymal Stromal Cells in Treating COVID-19 Acute Respiratory Distress Syndrome

“…Human MSCs do not express ACE2 receptors and resist infection ( 6 ). MSCs ( 7 ), or their extracellular vesicle-delivered microRNAs ( 8 ), reduce (SARS-CoV-2) proliferation in renal epithelial cell lines, but experimental studies of MSCs in COVID-19 pneumonia or ARDS are lacking. Experimental studies have tested the effects of MSCs on other viral pneumonia.…”